Makina opanga insulin

Insulin - mahomoni apachirengedwe omwe amawongolera | chakudya kagayidwe kake komanso kukhalabe wabwinobwino wa cazdpam'magazi. Kuperewera kwa mahomoni m'thupi kumatsogolera.) Ku matenda amodzi owopsa kwambiri - matenda ashuga, omwe, monga chifukwa cha imfayo, ali m'malo wachitatu pambuyo pa matenda amtima komanso khansa. Insulin ndi globule yaying'ono | Mapuloteni okhala ndi zotsalira za 51 amino acid zomwe zimakhala ndi ma polypeptide awiri omwe amaphatikizidwa ndi milatho iwiri yopanda malire. Amapangidwa mwanjira yofanana ndi unyolo wa fetal precursor, prroinsulin, wokhala koi peptide chapakati (ma 23 amino acid zotsalira) ndi cholumikizira 35 cholumikizira (C-peptide). Peptide ya siginolo ikachotsedwa, ma proinsulin omwe amatsalira 86 amino acid amapangidwa mu khungu, momwe ma A ndi B ma insulin amalumikizidwaC-neitweed, yomwe imawapatsa iwo mawonekedwe oyenera pa $ 3 pa disulfide bond. Pambuyo pang'onopang'ono wa proteinolytic wa C peptide, insulin imapangidwa.

Mitundu ingapo ya shuga imadziwika. Mawonekedwe owopsa kwambiri, ochizira omwe wodwala amafunikira matendawa (mawonekedwe a insulin - amadalira matenda), amayamba chifukwa cha imfa yosankha maselo opanga timadzi tating'onoting'ono tomwe timapanga timadzi tating'onoting'ono tambiri tomwe timapanga ma cell a Langerhans. Mtundu wa matenda a shuga, omwe mankhwala a insulin sawafunikira, ndi ochulukirapo, ungathe kuyendetsedwa mothandizidwa ndi zakudya zoyenera ndi:> ma. Nthawi zambiri, zikondamoyo za ng'ombe ndi ng'ombe sizimagwiritsidwa ntchito popanga nyama ndi kumalizira kumayamwa ndipo zimayikidwa m'ngolo zokutira m'makampani opanga mankhwala momwe amachotsa mahomoni. Kuti mupeze 100 g cr! Thulin lama insulin limafunikira 800-1000 kg za zowonjezera

Kuphatikizika kwa maunyolo onse ndi kulumikizana kwa maubwenzi awo a disudfid kuti apeze insulin kunachitika mu 1963 ndi 1965. magulu atatu ofufuza ku USA, China ndi Germany. Mu 1980, kampani yaku Danish Novo Corpri idapanga njira yosinthira insulini ya nkhumba kukhala insulin yaumunthu potenga zotsalira za 30 za alanine mu unyolo B ndi zotsalira za threonine. Onsewa a insulin sanasiyanane pakuchitika komanso nthawi yayitali.

Ntchito yopanga ma genulin opanga insulin inayamba zaka 20 zapitazo. Mu 1978, kunabwera uthenga wokhudza mtundu wa Escherichia coli wotulutsa ma proinsulin (USA). M'chaka chomwecho, maunyolo amtundu wa insulin amtundu wina adapangidwa mwakutanthauza ma genetic opanga ma cell.E.coli(Mkuyu. 5.11). Mtundu uliwonse wamtundu wopangidwa unapangidwa mpaka kumapeto kwa 3'-kumapeto kwa jini ya enzyme (3-galactosidase ndikulowetsedwa mu vector plasmid(pBR322).MaseloE.coliAnasinthidwa ndi mapuloteni oterewa, ma protein (amphongo) ophatikizidwa (chimeric) amapangidwa opanga chidutswa cha p-galactosidase ndi A kapena B insulin peptide yolumikizidwa kwa iye kudzera mwa zotsalira za methionine. Mukakonza puloteni ya chimeric ndi cyanogen bromide, peptide imamasulidwa. Komabe, kutsekeka kwa milatho yopanda malire pakati pa ma insulin omwe adapangidwa kunali kovuta.

Mu 1981, pro-insulin analogue, mini-C-pro-insulin, idapangidwa momwe 35-unit C-peptide idasinthidwa ndi gawo la ma amino acid: arg-arg-gly-ser-lys-arg ndipo mawu ake adawonetsedwaE.coli.

Mu 1980, W. Gilbert ndi anzake adasankha insulin mRNA kuchokera ku chotupa cha p-cell ya pancreatic ndipo adalandira CDNA kuchokera pamenepo pogwiritsa ntchito transcriptase. CDNA yomwe idayambika idayikidwa mu plasmidpBR322E.colimkati mwa genicillinase gene. Plasminant plasmid inali ndi chidziwitso cha kapangidwe ka proinsulin.Zotsatira za kutanthauzira kwa mRNA, mapuloteni osakanizidwa adapangidwa m'maselo omwe anali ndi penicillinase ndi proinsulin, omwe adapangidwa ndi trypsin kuchokera mu mapuloteni otere.

Mu 1978, ogwira ntchito ku Institute of Bioorganic Chemistry moyang'aniridwa ndi Acad. Yu. A. Ovchinnikov, majini apangidwe awiri omwe amapanga synthesis a neuropeptides anapangidwa:leucine- enkephalin ndi bradykinin.Jini wophatikizika wa leucine enkephalin anali ndi malembedwe “omata” awiri:

Jini yopanga yomwe idapangidwa idalumikizidwa limodzi ndi kachidutswa ka DNA mwachilengedwe komwe kumakweza ndi gawo la projeni la E. coli P-galactosidase proteinE.colikwa plasmid

Kupeza insulin, njira zamaumboni amtundu, Biotechnology - Coursework

1. kapangidwe ndi ntchito za insulin 5

1.1. Kapangidwe ka molekyulu 5

1.2. Kukula kwachilengedwe kwa insulin 7

1.3. Insulin Biosynthesis 8

2. genetic engineering insulin synthesis 10

2.1. Kugwiritsa ntchito njira zopangira ma genetic pakuphatikizidwa kwa mankhwala 10

2.2. Njira Zaukadaulo Zamtundu 11

2.3. Makina opanga insulin 14

Zotchulidwa pamawu

Komanso, zonsezi zimatha kupezeka nthawi imodzi munthawi ya mapuloteni osakanizidwa. Kuphatikiza apo, popanga mapuloteni a haibridi, mfundo zamaulidwe ochulukirapo zitha kugwiritsidwa ntchito - kupezeka kwa mitundu ingapo ya chandamale polypeptide mu mapuloteni osakanizidwa, omwe angakulitse kwambiri zipatso za chandamale.

Ku UK, zingwe zonse ziwiri za insulin yaumunthu zidapangidwa pogwiritsa ntchito E. coli, yolumikizidwa ndi molekyulu ya mahomoni ochita kupanga. Kuti chamoyo cha unicellular chizipanga mamolekyu a insulin pamapanga ake, ndikofunikira kuchipereka ndi pulogalamu yoyenera, ndiye kuti, kuyambitsa jini la mahormoni.

Insulin yothandizanso idapezedwa ku Institute of the Russian Academy of Sciences pogwiritsa ntchito majini opangidwa ndi ma genetic a E. coli. Mapuloteni a haibridi a hybrid amawonetsedwa kuchokera kuzomera zazomera, zomwe zimafotokozedwa zochuluka

40. mapuloteni onse okhala ndi ma protein omwe amakhala ndi prroinsulin.

Kutembenuka kwake kukhala insulin mu vitro kumachitika motsatizana monga mu vivo - polypeptide yotsogola imapukusidwa, preproinsulin imasinthidwa kukhala insulin kudzera m'magawo a oxidative sulfitolysis, kenako kutsekeka kutsekedwa kwa ma cell atatu osakanikirana ndikudzipatula kwa enzymatic kwa C-peptide yomanga. Pambuyo pamagulu angapo a ion-exchange, gel ndi HPLC chromatographic kuyeretsa, insulin yaumunthu yodziyeretsa komanso zochitika zachilengedwe zimapezeka.

Kuti mupeze insulini, kupanikizika kumagwiritsidwa ntchito ndi zotsatizana za nucleotide zomwe zimayikidwa mu plasmid ndikuwonetsa mapuloteni osakanizidwa okhala ndi proinsulin yotsogola komanso kachidutswa ka protein ya Staphylococcus aureus A yomwe yaphatikizika ndi N-terminus kudzera mwa zotsalira za methionine 8, 9, 10.

Kulima kwa saturated biomass yama cell a recombinant kupanikizana kumapereka chiyambi cha kupanga mapuloteni osakanizidwa, kudzipatula ndikusinthidwa komwe mu chubu kumabweretsa insulin.

Njira inanso ndiyothekanso: kupeza mu bakiteriya dongosolo losonyeza mapuloteni obwerezabwereza omwe amakhala mchira wa proinsulin ndi polyhistidine wophatikizidwa ndi iyo yotsalira ya methionine. Iparayi imagwiritsa ntchito chelate chromatography pamizati ndi Ni-agarose ndi bromine cleavage.

Mapuloteni apadera ndi S-sulfonated. Kuwona mapu ndi kuwunika kwakuwonekera kwa proinsulin yoyeretsedwa ndi ion kusinthana ndi chromatography pa anion exchange resin ndi RP (gawo losinthika) gawo lalikulu lamadzimadzi liziwonetsa kukhalapo kwa milatho yopanda tanthauzo ya milatho yama proinsulin yakumunthu.

Posachedwa, chidwi chachikulu chaperekedwa kuti njira zosavuta zopangira insulin zithandizenso mwa kuyambitsa majini.Mwachitsanzo, mutha kupeza puloteni yokhala ndi proinsulin yolumikizidwa kwa N-terminus kudzera pazotsalira za mtsogoleri wa peptide wa interleukin

2. Mapuloteni akuwonetsedwa bwino ndikuwonekera pamatupi ophatikizika. Pambuyo podzipatula, mapuloteni opanga insulin ndi C-peptide amamangidwa ndi trypsin 5, 8, 10.

Insulin yoyambitsa ndi C-peptide imayeretsedwa ndi RP-HPLC. Chofunikira kwambiri pakupanga zida zophatikizidwa ndizofanana ndi kuchuluka kwa mapuloteni onyamula ndi polypeptide.

C-peptides ogwiritsa ntchito amino acid spacers onyamula malo a Sfi I oletsedwa komanso zotsalira ziwiri za arginine koyambirira koyambira ndi kumapeto kwa spacer kwa mapuloteni omwe adagawanika ndi trypsin, amalumikizidwa molingana ndi mfundo ya mchira wamutu.

HPLC yazogulitsa zowoneka bwino ikuwonetsa kuti kujambulidwa kwa C-peptide kumachitika zochulukirapo, ndipo izi zimathandiza kugwiritsa ntchito majini opanga amitundu yambiri kuti apange polypeptides chandamale pamsika wamafuta.

Pomaliza

Zosasinthika, ndipo nthawi zambiri, njira yokhayo yosungitsira moyo ndi ntchito ya odwala omwe ali ndi matenda osokoneza bongo ndi lero, insulin.

Asanalandire ndikulowetsa insulini m'machitidwe azachipatala, zotsatira zoyipa zimayembekezeredwa kwa chaka chimodzi kapena ziwiri kuyambira pachiwonetsero cha matenda a odwala I amtundu wa shuga, ngakhale atagwiritsa ntchito zakudya zofooketsa kwambiri.

Odwala a Type I a shuga amafunikira chithandizo chanthawi yonse cha mankhwala a insulin. Kuchepetsa kwa kayendetsedwe ka insulin nthawi zonse pazifukwa zina kumabweretsa kukula kwovuta komanso kufa mwachangu kwa wodwalayo.

Pakadali pano, kuchuluka kwa matenda ashuga kuli malo achitatu pambuyo pa matenda a mtima ndi zotupa. Kukula kwa matenda ashuga pakati pa akulu, malinga ndi World Health Organisation, m'malo ambiri padziko lapansi ndi 2-5% ndipo amayamba kuchuluka

Zaka 1.% za kuchuluka kwa odwala pafupifupi. Chiwerengero cha odwala omwe akudalira insulin, ngakhale akupita patsogolo pantchito zaumoyo, chikuchulukira chaka chilichonse, ndipo ku Russia kokha kuli anthu pafupifupi 2 miliyoni.

Njira zabwino kwambiri zopangira insulin ndi njira zopangira ma genetic. Insulin yopanga ma genetically imapezeka ndi ma cell awiri opanga A ndi B pogwiritsa ntchito molekyulu osiyanasiyana, ndikutsatiridwa kwa isoforms, komanso kaphatikizidwe ka proinsulin m'maselo a E. Coli omwe amakhala ndi khungu la trypsin ndi carboxypeptidase.

Kupanga makina opanga ma insulin opangidwa ndi chibadwa cha anthu kumatsegulira njira zatsopano zothetsera mavuto ambiri a matenda ashuga a ku Russia kuti apulumutse miyoyo ya anthu mamiliyoni ambiri odwala matenda ashuga.

Zolemba

Balabolkin M.I., Klebanova E.M., Kreminskaya V.M. Matenda a shuga: njira zamakono zakuzindikiritsa ndi kuchiza / Dokotala, ed. G.L. Vyshkovsky.-2005.- M: RLS-2005, 2004.- 960 p.

Gavrikov, A.V. Kukhathamiritsa kwa biotechnological kupanga zinthu za recombinant human interferon: dis. ... maswiti. biol. Sayansi - M, 2003

Majini amapanga insulin yaumunthu. Kuchulukitsa mphamvu ya kupatukana kwa chromatographic pogwiritsa ntchito mfundo ya bifunctionality. / Romanchikov A.B., Yakimov S.A., Klyushnichenko V.E., Arutunyan A.M., Wulfson A.N. // Bioorganic Chemistry, 1997 - 23, Na. 2

Glick B., Pasternak J. Kuwongolera kagwiritsidwe ntchito ka njira zamaukadaulo // B. Glick, J. Parsnip / Molecular Biotechnology = Molecular Biotechnology. - M: Mir, 2002 .-- S. 517-532. - 589 p.

Glick B., Pasternak J. Molecular Biotechnology. Mfundo ndi magwiritsidwe ake. M: Mir, 2002.

Davis R., Botstein D, Roth J. Njira zakugwiritsira ntchito ma genetic. Ma genetics a bacteria // R. Davis, D. Botstein, J. Roth / Per. kuchokera ku Chingerezi.-M .: Mir. - 1984.— 176 p.

Ermishin A.P.Zamoyo Zosinthidwa Mwa Chibadwa: Nthano ndi Zenizeni / A.P. Ermishin // Mn.: Tekhnalogaliya.— 2004. - 118 p.

Mfundo Zazikulu Zapulogalamu Yopanga Zamankhwala: Textbook / TP Prischep, V.S. Chuchalin, K.L. Zaykov, L.K. Mikhaleva. - Rostov-on-Don.: Phoenix, Tomsk: NTL Publishing House, 2006.

Patrushev L.I. Magulu opanga ma genetic. // L.I. Patrushev / M: Nauka.— 2004.

Romanchikov, A.B. Majini amapanga insulin yaumunthu. Kuchulukitsa mphamvu ya kupatukana kwa chromatographic pogwiritsa ntchito mfundo ya bifunctionality. / A.B. Romanchikov ndi ena.

// Bioorganic Chemistry. 1997. Ayi. 2 p. 23

Rybchin V.N. Mfundo Zachidziwitso cha Genetic Engineering // V.N. Rybchin / 2nd ed., Revised. ndipo onjezerani: Buku lalemba ku mayunivesite. SPb: Kusindikiza nyumba ya SPbSTU. - 2002 .-- 522 s.

Schelkunov S. N. Kanjinoloji wa majini // Schelkunov S. N. / Novosibirsk: Sib. univ. Nyumba Yosindikiza. 2008.

Schelkunov, S.N. Umisiri wamtundu: zolemba. chilolezo. - 2nd, ed., Chiv. ndi kuwonjezera. - Novosibirsk: Sib. univ. Nyumba Yofalitsa, 2004 .-- 496 p.

1. Komwe kuli ma disulfide ma cell mu molekyulu ya insulin.

2. Makonzedwe a amino acid amatsala mu molekyulu ya insulin

Zotsatira za insulin pazinthu zazikulu za michere

Chiwindi minofu Adipose minofu activation 1. Phosphodiesterase 1. Phosphodiesterase 1. LP-lipase

4. Pyruvate dehydrogenase zovuta

5. Phosphatase glycogen synthase ndi glycogen phosphorylase

5. Glycogen synthase phosphatase b. Acetyl-CoA-carboxylase Induction 1. Glucokinase 1. Glyceraldehyde phosphate dehydrogenase

6. Glucose-6-phosphate dehydrogenase Repression Phosphoenolpyruvate carboxykinase

Mkuyu. 3 Chiwembu cha insulin biosynthesis mu β-maselo a islets a Langerhans. ER - endoplasmic reticulum. 1 - kapangidwe ka peptide ya chizindikiro, 2 - kaphatikizidwe ka preproinsulin, 3 - mawonekedwe a peptide, 4 - kutengera kwa proinsulin kupita ku zida za Golgi, 5 - kutembenuza kwa proinsulin kupita ku insulin ndi C-peptide komanso kuphatikizidwa kwa insulin ndi C-peptide kukhala zigawo zazinsinsi, 6 - insulin ndi C peptide.

4. Chiwembu chambiri cha kapangidwe ka insulin kuchokera kwa otsogolera

Mkuyu. Kaphatikizidwe ka insulin popanga maunyolo awiri osiyana

Njira yopezera chibadwa cha insulin ya anthu

Zomwe zimapangidwazo zimakhudzana ndi gawo la sayansi ya zamankhwala, makamaka pakupanga insulin yaumunthu yopanga majini yopanga mankhwala omwe amagwiritsidwa ntchito pochiza matenda osokoneza bongo.

Njirayi imagwiridwa ndikupanga cholembera wopanga mapuloteni osakanizidwa okhala ndi ma proinsulin a anthu, Escherichia coli BL21 / pPINS07 (BL07) kapena Escherichia coli JM109 / pPINS07, akuwononga maselo mwa kudzipatula, kulekanitsa matupi okhala ndi mapuloteni osakanizidwa.

Chotsatira, kutsuka koyambirira kwa matupi ophatikizika, kuwononga nthawi yomweyo mapuloteni ndi kubwezeretsa zomangira zosagwirizana mu buffer ndi 5-10 mM dithiothreitol ndi 1 mM EDTA kumachitika, kukonzanso komanso kuyeretsa mapuloteni osinthidwa a fusion ndi ion kusinthanitsa ndi chromatography.

Kutalika kwa mapuloteni osakanizidwa kumachitika ndi kuphatikiza kwa hydrolysis ya trypsin ndi carboxypeptidase B pa kulemera kwake kwa mapuloteni osakanizidwa, trypsin ndi carboxypeptidase B 4000: 0.6: 0.9.

Kuyeretsa kwa insulin kumachitika ndi hydrophobic chromatography kapena kusintha gawo lalikulu lamadzimadzi amadzimadzi amatsatiridwa ndi kusefera kwa gel, komanso kudzipatula kwa insulini ndi crystallization pamaso pa zinc. Kupanga kumeneku kumathandizira kuchepetsa njira yopezera ma insulin omwe amapangidwa ndi anthu ndikuwonjezera zomwe akutulutsa.

Poganizira zomwe zikuluzikulu za matenda ashuga amakono komanso malingaliro a World Health Organisation, mayiko aku Europe pofika 2001 adamaliza kusintha kwa kugwiritsa ntchito insulin ya anthu. Pankhaniyi, kupanga njira zopangira insulin pogwiritsa ntchito njira zaukadaulo wa DNA ndi ntchito yofunika kuchitapo kanthu mwachangu.

Njira yodziwika yopangira ma insulini opangidwa ndi chibadwa cha anthu, yomwe imakhala ndikupanga mtundu wopanga E. Coli kupanga proinsulin, yokhala ndi magawo awiri a zomanga thupi a IGG a protein ya staphylococcal A.

Njira imakhala ndikuwononga maselo a bakiteriya, kuphatikiza Taurus yophatikiza proinsulin, kuphatikiza kuphatikizika Taurus, oxidative sulfitolysis ya proinsulin, kukonzanso kwake, kuyeretsa kwa mapuloteni osinthika ndi ma prooper chromatography, kufotokozera kwa Proinsulin ndi michere ya proteinolytic (kuyerekeza ndi carboxypeptidase purosesa yotsimikizika ya kuyeretsa kwakukulu chromatography (Nilson J., Jonasson P., Samuelsson E., Stahl S., Uhlen M. "Kuphatikiza kuphatikiza kwa insulin ya anthu ndi C-peptide yake", Journal of biotechnology, 1996, v. 48, p. 241-250) .

Zoyipa za njirayi ndizokwera mtengo kwa malonda ndi kugwiritsidwa ntchito popanga insulin, zomwe zingakhalepo pazomwe mukufuna.

Njira yodziwika yopanga ma insulin yaumunthu, yomwe imapangira maselo a omwe amapanga E.

Coli DN5 a / pVK100, kuwononga maselo mabakiteriya ndi kupendekeka, kupatula matupi ophatikiza omwe amakhala ndi mapuloteni osakanikirana ndi zinthu zosasungunuka zamadzimadzi ndi centrifugation, sinthani matupi ophatikizira mu buffer yomwe ili ndi 8 M urea, 1 mM dithiothreitol, 0 M Mrisris HCl, pH 8.0, kwa maola 12-16.

Zitsulo zopanda kanthu zimachotsedwa ndi centrifugation, pambuyo pake ndende ya dithiothreitol imachulukitsidwa mpaka 10 mM ndipo ma disulfide bond amabwezeretsedwa pa 37 ° C kwa ola limodzi. Njira yothetsera vutoli idapakidwa kasanu ndi madzi ozizira, osinthidwa ndi pH 4.5 ndikuwumbika kwa maola 2 pa 4 ° C kuti ipange mpweya.

Pulogalamu yokhala ndi mapuloteni osakanizidwa idasiyanitsidwa ndi centrifugation ndikuisintha, kusungunuka mwachangu m'madzi ozizira pa pH ya 10-12, pambuyo pake idasungunuka ndi 10 mM glycine buffer, pH 10.8, ndikuisungidwa mpaka 4 ° C usiku. Pambuyo pakupanga, njira yothetsera vutoyi idayatsidwa ndi gel osasankhidwa pa mzere wa Sephadex G-50 ndikuwonjezera ndi 10 mM glycine buffer.

Tizigawo ting'onoting'ono timene timaphatikizidwa, timatumba, ndipo timauma. Mapulogalamu obwera chifukwa cha fusion amasungunuka mu 0,88 M Tris-HCl buffer, pH 7.5, mpaka m'magazi a 10 mg / ml ndipo atakonzedwa nthawi yomweyo ndi trypsin ndi carboxypeptidase B (chiyerekezo cha carboxypeptidase B: trypsin: fusion protein 0,3: 1: 10) pa 37 ° C kwa mphindi 30.

Kenako onjezani isopropanol 40%. Kusakaniza uku kujambulidwa pachithunzithunzi cha DEAE-Sephadex A-25 ndikuwongolera ndi 0.05 M Tris-HCl buffer, pH 7.5 ndi 40% isopropanol yokhala ndi mzere wowoneka bwino wa sodium chloride kuchokera 0 mpaka 01. Pambuyo kuchotsa isopropanol, ndende ya sodium chloride. onjezerani ku 25%, sinthani pH ku 2.0 ndikusonkhanitsa insulin.

(Chen J.Q., Zhang H.T., Hu M.N., Tang J.-G., "Kupanga kwa insulin kwa anthu mu dongosolo la E. Coli ndi ma-pro-lys-human proinsulin monga momwe akufotokozera owongolera "Anagwiritsa Ntchito Biochemistry and Biotechnology, 1995, v. 55, p. 5-15).

Zoyipa za njirayi zimaphatikizapo kugwiritsidwa ntchito kwa kusefera kwa gel m'magawo oyamba, omwe amafunikira kuchuluka kwa sorbent ndi kuchuluka kwa ma enzymes omwe amagwiritsidwa ntchito mu cleavage mapuloteni osakanizidwa.

Njira yodziwika yopangira ma insulini opangidwa ndi chibadwa cha anthu, kuphatikiza chopanga chopanga cha Escherichia coli JM109 / pPINS07, ndikuwononga mabakiteriya mwa kudzipatula, kulekanitsa matupi omwe amaphatikiza mapuloteni osakanizidwa, kuwasungunula ndikumayeretsa purosesa yoyeserera kuchuluka kwa zodetsa zophatikizika mu 40% isopropanol kutsatiridwa ndi chromatografia pa KM-sepharose, kufalikira kwake kotsatana ndi trypsin ndi carboxypeptidase B, pomwe katunduyo trypsinolysis ikujambulidwa pa SP-Sepharose, yolingana ndi 0,03-0.1 M ammonium acetate buffer pH 5.0-6.0 yokhala ndi 6 M urea, yokhala ndi mapuloteni otsekemera ndi mzere wowoneka bwino wa sodium chloride kuchokera pa 0 mpaka 0,5 M poyambira. buffer, ndipo kachigawo ka insulin komwe kamene kamapezeka ndi carboxypeptidase B kanayeretsedwa ndikusinthanso gawo lalikulu lamadzimadzi amadzimadzi (RP HPLC) lotsatiridwa ndi gel kusefera (Pat. RF No. 2141531, MKI C12P 21/02, Publ. 1999)

Zoyipa za njirayi zimaphatikizapo kugwiritsa ntchito kuchuluka kwa urea ndi ma organic sol sol panthawi yotsuka mapuloteni osakanizidwa.

Katswiri wa matenda ashuga

Musanagwiritse ntchito insulin, moyo wodwala wokhala ndi matenda osokoneza bongo anali osaposa zaka 10. Kupangidwa kwa mankhwalawa kwapulumutsa odwala ambiri. Insulin yomanga yaumunthu ndi kupita patsogolo kwapamwamba kwambiri kwasayansi.

Zotsatira za zaka zambiri zolimbikira

Asanayambe kupanga ma genetic engineering (recombinant), insulin inali itapatula nkhumba za ng'ombe ndi nkhumba.

Kusiyana pakati pa insulin ya insulin ndi munthu ndi amino acid imodzi

Zoyipa za njira iyi yopezera mankhwalawa:

zovuta zosungira komanso zoyendetsa zinthu zachilengedwe,
kusowa kwa ziweto
zovuta zomwe zimakhudzana ndikugawidwa komanso kuyeretsedwa kwa mahomoni a pancreatic,
chiopsezo chachikulu cha thupi siligwirizana.

Ndi kapangidwe ka insulin yaumunthu mu bioreactor mu 1982, nthawi yatsopano yopanga zinthu zachilengedwe inayamba. Ngati mbandakucha wa mankhwala a insulin, cholinga cha asayansi chinali kupulumuka kwa wodwalayo, munthawi yathu ino kupanga mankhwala atsopano ndikulimbana ndi kulipiritsa chindapusa cha matendawa. Cholinga chachikulu cha kafukufuku wasayansi ndikupanga moyo wabwino wa wodwala wodwala matenda ashuga.

Ukadaulo wamakono

Mitundu ya mankhwala, kutengera njira yokonzekera:

Majini a Kubwezeretsa

Pazopangidwe, geni yomwe yasinthidwa ka geni imagwiritsidwa ntchito.

kusowa kwa mayankho
kupanga mwaluso,
kuchuluka kwa kuyeretsa.

Wokondedwa wa geneticists ndi E. coli

Kusinthidwa Mtundu

Zolemba zoyambira ndi insulin. Amasinthidwa ndi njira yololera.

Kapangidwe ka Hormone

Zopanga

Mankhwala opangidwa ngati, opangidwa, ali ofanana kwathunthu ndi insulin yaumunthu.

Kupanga mankhwala

Chimachitika ndi chiani m'thupi pambuyo pakumwa mankhwala?

Kulumikizana ndi receptor of membrane cell, insulin imapanga zovuta zomwe zimakwaniritsa izi:

Zimasintha kayendedwe kabwino ka glucose ndikuthandizira kuyamwa kwake.
Imalimbikitsa kumasulidwa kwa ma enzymes omwe amathandizira pokonza shuga.
Imachepetsa kuchuluka kwa mapangidwe a glycogen mu chiwindi.
Imathandizira mafuta ndi kagayidwe kazakudya.

Pankhani ya subcutaneous makonzedwe, insulin amayamba kuchita mphindi 20-25. Kutalika kwa mankhwalawa kuchokera kwa maola 5 mpaka 8. Imakonzedwanso ndi enzyme insulinase ndipo imatuluka mkodzo. Mankhwala samadutsa placenta ndipo samadutsa mkaka wa m'mawere.

Kodi insulin yomwe imapangidwa ndi chibadwa imayikidwa liti?

Ngati thandizo likufunika

Mtundu wa insulin wopangidwa ndi anthu umagwiritsidwa ntchito milandu:

Lembani 1 kapena matenda ashuga 2. Amagwiritsidwa ntchito ngati chithandizo chodziimira pawokha kapena kuphatikiza ndi mankhwala ena.
Ndi kukana kwa m`kamwa hypoglycemic wothandizira.
Ndi matenda ashuga mwa amayi apakati.
Pazovuta za impso ndi chiwindi.
Mukayamba kusungunulira insulin.
Mu nthawi ya ntchito.
Pankhani ya zochitika zakupha (hyperosmolar or ketoacidotic coma).
Panthawi zadzidzidzi (musanabadwe mwana, ndimavulala).
Ngati pali zotupa za khungu la dystrophic (zilonda zam'mimba, furunculosis).
Chithandizo cha matenda osokoneza bongo motsutsana ndi matenda.

Ma insulin opanga ma genetic a anthu amalekeredwa bwino ndipo samayambitsa zovuta, chifukwa ndizofanana ndendende ndi mahomoni achilengedwe.

Kuwunikira nthawi zonse ndikofunikira!

Sizoletsedwa kupereka mankhwala ngati:

kutsitsa shuga
Hypersensitivity mankhwala.

M'masiku oyambira pambuyo pa kuperekedwa kwa mankhwalawa, kuyang'anira wodwala ndikofunikira.

Zotsatira zoyipa

Kuopsa kwa Urticaria! Quincke's edema!

Nthawi zina, mukamagwiritsa ntchito insulin, zovuta zotsatirazi ndizotheka:

thupi lawo siligwirizana (urticaria, edema ya Quincke, kuyabwa kwa khungu),
kuchepa kwakukulu kwa shuga m'magazi (kumayamba chifukwa chokana mankhwalawa ndi thupi kapena poti pakukangana).
chikumbumtima
muzovuta kwambiri, kukulitsa kwa hypoglycemic coma ndikotheka,
ludzu, kamwa yowuma, ulesi, kulephera kudya.
hyperglycemia (mukamagwiritsa ntchito mankhwalawo motsutsana ndi matenda oyambitsidwa ndi matenda kapena malungo),
khungu
zimachitika mdera la oyang'anira (kuwotcha, kuyabwa, kuwonda kapena kuchuluka kwa mafuta ochulukirapo).

Nthawi zina kuzolowera mankhwala kumayendera limodzi ndi zovuta monga kutupa ndi kuwonongeka kwa mawonekedwe. Mawonetsedwe awa nthawi zambiri amatha patatha milungu yochepa.

Momwe mungapezere insulin yopanga ma genetic?

Mankhwalawa amapezeka mu njira yothetsera makolo makonzedwe:

"Biosulin"	Kutalika kwachitidwe
Khalid	Mwachidule kuchita insulin
Gensulin	Kukonzekera kwa Biphasic (kuphatikiza ma insulin aafupi komanso apakati)
Rinsulin	Zotsatira zake
Humalog	Khola la syringe limagwiritsidwa ntchito popereka mankhwalawo.

Sikovuta kusankha kukonzekera kwa insulin poganizira zomwe wodwalayo ali nazo.

Migwirizano yamagwiritsidwe

Nthawi zambiri, subulinaneous insulin imagwiritsidwa ntchito.

Mwadzidzidzi, mankhwalawa amaperekedwa.

Woopsa wodwala

Ngakhale munthu wodwala matenda ashuga amatha kulakwitsa pogwiritsa ntchito mankhwalawa.

Popewa zovuta, ndikofunikira:

Musanagwiritse ntchito, yang'anani tsiku lomwe linatha.
Onani malangizo osungira: Mbale zoyikira ziyenera kusungidwa mufiriji. Vial yomwe yakonzedwa imatha kusungidwa m'malo otentha kwambiri m'malo abata.
Onetsetsani kuti mwakumbukira mlingo woyenera: werenganinso zomwe dokotala analemba.
Pamaso jakisoni, ndikofunikira kumasula mpweya kuchokera ku syringe.
Khungu liyenera kukhala loyera, koma osayenera kumwa mowa pakakonzedwe, chifukwa limachepetsa mphamvu ya mankhwalawa.
Sankhani malo abwino kwambiri obayira. Akayambitsidwa pansi pakhungu la pamimba, mankhwalawa amachita mofulumira. Kuchepetsa pang'onopang'ono kwa insulin mukamayambitsa khola kapena phewa.
Gwiritsani ntchito dera lonse lapansi (kupewa mavuto amderalo). Mtunda pakati pa jakisoni uyenera kukhala wosachepera 2 cm.
Gwirani khungu pakhungu kuti muchepetse ngozi yolowera minofu.
Ikani syringe pansi pakhungu pakona kuti mankhwalawo asatayike.
Pakulowetsedwa m'mimba, insulin yochepa imaperekedwa mphindi 20 asanadye. Mukasankha paphewa kapena matako - mphindi makumi atatu musanadye.

Kuphatikiza ndi mankhwala ena

Nthawi zambiri wodwala matenda ashuga, wodwala amatenga mankhwala angapo. Kuphatikizidwa ndi mankhwala ena kungakhudze achire zotsatira za insulin.

Popewa zovuta, muyenera kudziwa:

Onjezerani zovuta za insulin yopanga ma genetic pochepetsa shuga	Sulfonamides. Mao inhibitors (furazolidone). ATP inhibitors (Captopril). Nonsteroidal anti-kutupa (diclofenac, aspirin). Androgens. Mankhwala a Antimalarial (quinidine). Anabolic steroids. Tetracycline antibayotiki (doxycycline). Theofylline. Morphine.	Mankhwala otchuka omwe amagwiritsidwa ntchito pochiritsa matenda a kwamikodzo thirakiti Doxycycline
Kuchepetsa insulin	Glucocorticoids (prednisone, hydrocortisone). Zomwe zili ndi estrogen za pakamwa. Zodzikongoletsera Amphetamines. Mahomoni a chithokomiro. Sympathomimetics (adrenaline, mesatone, dopamine). Glucagon.	Tcherani khutu!

Bongo

Nthawi zina, kayendetsedwe ka insulini kumapangitsa kuchepa kwa shuga m'magazi. Vutoli nthawi zambiri limadza chifukwa chosankhidwa mosayenera.

Zizindikiro zoyambirira za hypoglycemia:

kufooka
kukopa kwa pakhungu
nkhawa boma
chizungulire
chisokonezo
dzanzi mikono, miyendo, lilime ndi milomo,
miyendo yanjenjemera
thukuta lozizira
kumva kwamphamvu njala
mutu.

Kuwonongeka kwadzidzidzi

Ngati muzindikira kuti muli ndi vuto loteroli, muyenera kudya mwachangu zakudya zokhala ndi michere yamagetsi. Itha kukhala ma cookie, maswiti, chidutswa cha shuga kapena mikate yoyera. Tiyi wokoma amathandizira pazinthu zotere.

Ngati matendawo akuipiraipira, muyenera kuyimbira ambulansi. Hypoglycemia ingayambitse kudwala kapena kufa kwa wodwala.

Kodi kubwerezanso insulin?

Moni Insulin yothandizanso siyosiyana ndi zachilengedwe. Kuti mupeze, mabakiteriya omwe amasinthidwa mwanjira amagwiritsidwa ntchito.

Pogwiritsa ntchito matekinoloje opanga ma genetic, DNA yongobwereranso yomwe imakhala ndi insulini imayikidwa mu khungu la E. coli. Zamoyo zosinthidwa mwachilengedwe zimachulukana ndikupanga mahomoni. Mankhwalawa ndi othandiza kwambiri komanso amakhala ndi kuyeretsa kokwanira.

Insulin Gawo II Kupanga insulin

gawo loyanjana - zimathandizira kwambiri kudzipatula kwa mapuloteni osakanizidwa.

Potere, zonsezi zimatha kupezeka nthawi imodzi mu kapangidwe ka mapuloteni osakanizidwa.

Kuphatikiza apo, popanga mapuloteni a haibridi, mfundo zamaulidwe ochulukirapo zitha kugwiritsidwa ntchito (ndiye kuti, mapepala angapo a polypeptide omwe amapezeka amapezeka mu mapuloteni osakanizidwa), omwe angakulitse kwambiri zipatso za chandamale.

2 Kulimbikitsa kwa proinsulin m'maselo a E. coli ..

Mu ntchitoyi, olemba adagwiritsa ntchito JM 109 N1864 yokhala ndi nucleotide yolembedwa mu plasmid ikuwonetsa mapuloteni osakanizidwa, omwe amakhala ndi proinsulin yotsogola ndi kachidutswa ka protein ya Staphylococcus aureus A yomwe yaphatikizidwa ndi N-terminus yake kudzera mwa zotsalira za methionine.

Kulima kwa saturated biomass yama cell a recombinant kupanikizana kumapereka chiyambi cha kupanga mapuloteni osakanizidwa, kudzipatula ndikusinthidwa komwe mu chubu kumabweretsa insulin.

Gulu lina la ofufuza adalandira mapuloteni oyeneranso mu dongosolo la bakiteriya lomwe limapangidwa ndi proinsulin yaumunthu ndi mchira wa polyhistidine wophatikizidwa ndi iwo mwa methionine yotsalira. Idali yokhayokha pogwiritsa ntchito chelate chromatography pamizati ya Ni-agarose kuchokera ku matupi ophatikizika ndikugayidwa ndi cyanogen bromide.

Kuwona mapu ndi kuwunika kwakuwonekera kwa proinsulin yoyeretsedwa ndi ion kusinthana ndi chromatography pa anion exchange resin ndi RP (gawo losinthika) HPLC (kuchuluka kwa madzi amadzimadzi a chromatography) iwonetsa kukhalapo kwa milatho yopanda tanthauzo yogwirizanitsa milatho yama proinsulin achibadwa. Pepala limanenanso za kukhazikitsidwa kwa njira yatsopano, yosinthika yopangira insulin yaumunthu pakupanga ma genetic mainjini a prokaryotic. Olembawo adawona kuti insulini yomwe idapangidwa mu kapangidwe kake ndi zochita zake zimakhala zofanana ndi mahomoni opatulidwa ndi kapamba.

Posachedwa, chidwi chachikulu chaperekedwa kuti njira zosavuta zopangira insulin zithandizenso mwa kuyambitsa majini. Chifukwa chake, alembawo adapeza mapuloteni ophatikizika a peptide ya interleukin 2 yolumikizidwa ndi N-terminus ya proinsulin kudzera pazotsalira za lysine.

Mapuloteni adawonetsedwa bwino ndikuwonetsedwa pamatupi ophatikizika. Pambuyo podzipatula, mapuloteniwo adamugaya ndi trypsin kuti apange insulin ndi C-peptide. Gulu lina la ofufuza linachitanso chimodzimodzi.

Mapuloteni ophatikizika okhala ndi proinsulin komanso magawo awiri opanga a staphylococcus Puloteni yomanga IgG idapangidwa pamatupi ophatikizidwa, koma inali ndi mawonekedwe apamwamba. Mapuloteniwa adadzipatula ndi ma membrane chromatography amagwiritsa ntchito IgG ndikukonzedwa ndi trypsin ndi carboxypeptidase B.

Insulin yoyambitsa ndi C-peptide anayeretsedwa ndi RP HPLC. Mukamapanga zida zopangidwa, kuchuluka kwa mapuloteni onyamula ndi polypeptide yoyambira ndikofunikira kwambiri.

Chifukwa chake, ntchitoyi imalongosola zomanga zomanga thupi, momwe mapuloteni omanga thupi a seramu adagwiritsidwa ntchito ngati polypeptide. Amodzi, atatu ndi asanu ndi awiri a C-peptides adalumikizidwa nawo.

C-peptides anali olumikizidwa pamutu-mchira pogwiritsa ntchito amino acid spacers onyamula malo a Sfi I oletsedwa komanso zotsalira ziwiri za arginine koyambirira koyambira ndi kumapeto kwa spacer kwa mapuloteni omwe adagawika ndi trypsin. HPLC yazogwiritsa ntchito cleavage idawonetsa kuti mawonekedwe a C-peptide ndi ochulukirapo, ndipo izi zimalola kugwiritsa ntchito majini opanga amitundu yambiri kuti apeze polypeptides omwe akufuna.

Ntchitoyi ikufotokoza kukonzekera kwa proinsulin mutant, yomwe inali ndi kusintha kwa Arg32Tyr. Puloteniyu ataphatikizidwa ndi trypsin ndi carboxypeptidase B, insulin yachilengedwe komanso C-peptide yokhala ndi zotsalira za tyrosine zidapangidwa. Wotsirizirayi, atalemba zilembo za 125I, amagwiritsidwa ntchito mwachangu mu radioimmunoassay. 3 kuyeretsa insulin.

Insulin yopangira mankhwala ayenera kukhala oyera. Chifukwa chake, kuyang'anira kwachangu kwazomwe zimapangidwa pagawo lililonse la kupanga ndikofunikira. M'mbuyomu, RP ndi IO (ion exchange) HPLC idagwiritsidwa ntchito popanga proinsulin-S-sulfonate, proinsulin, munthu A- ndi B-maunyolo, ndi ma S-sulfonates awo.

Chidwi chachikulu chimaperekedwanso kwa fluorescent insulin. Mu ntchitoyi, olemba adafufuza momwe ntchito ikuyendera ndi kuphunzitsika kwa njira za chromatographic pakuwunika kwa magawo onse amtundu wa insulin yopanga anthu ndipo adapanga ndandanda ya magwiridwe antchito a chromatographic kuti athe kudzipatula ndikuwonetsa zinthu zomwe zimadza.

Kuphatikiza apo, njira zikupangidwa kuti zizigwiritsa ntchito kuti zizigwiritsa ntchito moyenera komanso zimathandizira njira zodziwitsira kuyera ndi kuchuluka kwa insulini.

Chikalatacho chimafotokoza za kafukufuku wa kuthekera kwa kugwiritsa ntchito RP yamadzi chromatography ndikuyang'ana kwa electrochemical pakutsimikiza kwa insulin, ndipo njira yotsimikizirira insulini yotalikirana ndi chisumbu cha Langerhans ndi immunoaffinity chromatography yodziwika ndi spectrometric.

Ntchitoyi, kuthekera kwa kugwiritsa ntchito mwachangu-kutsimikiza kwa insulini pogwiritsa ntchito capillary electrophoresis yodziwika ndi laser-fluorescence kunasanthulidwa. Kusanthula kumachitika powonjezera pa sampule kuchuluka kwa insulin yolembedwa ndi phenylisothiocyanate (FITC) ndi chidutswa cha Fab cha monoclonal insulin antibodies. Yolembedwa komanso yolimbitsa thupi nthawi zonse imachita nawo mpikisano wa Fab. FITZ-yokhala ndi insulini yokhala ndi insulin komanso zovuta zake ndi Fab zimalekanitsidwa m'masekondi 30.

Posachedwa, ntchito zambiri zakhala zikuchitika pakukonzanso njira zopangira insulin, komanso kupanga mitundu ya zipatso kutengera izi.

Mwachitsanzo, ku USA, hepatospecific insulin analogs ali ndi patent, yosiyana mwachilengedwe ndi mahomoni achilengedwe chifukwa chobweretsa mitundu yotsalira ya amino acid pamipando ya 13 ndi 19 ya Chingwe ndi pamalo 16 a mnyolo wa B.

The analogues omwe amagwiritsidwa ntchito osiyanasiyana parenteral (intravenous, intramuscular, subcutaneous), intranasal Mlingo mitundu kapena kulowetsedwa m'njira yapadera kapisozi mankhwalawa matenda a shuga. Chofunika kwambiri ndikupanga mitundu ya mitundu yoperekedwa popanda jakisoni.

Pepalalo limanenanso za kupangidwa kwa makina olimbitsa mtima a macromolecular, omwe amathandizira insulini mu voliyumu ya polymer hydrogel yosinthidwa ndi mapuloteni a puloteni enzyme. Kugwiritsa ntchito mankhwala koteroko ndi 70-80% ya mphamvu ya subcutaneily yoyambitsa insulin.

Mu ntchito ina, mankhwala amapezeka ndi insulation imodzi ya insulin yokhala ndi maselo ofiira am'magazi, omwe amatengedwa muyezo wa 1-4: 100, pamaso pa wothandizira.Olembawo akuti adalandira mankhwala omwe ali ndi zochita za mayunitsi a 1000 / g, kusungidwa kwathunthu kwa ntchito pambuyo pakulamula pakamwa ndi kusungidwa kwa zaka zingapo mu mawonekedwe a lyophilized.

Kuphatikiza pakupanga mitundu yatsopano ya mankhwala ndi mitundu ya mankhwalawa kutengera insulin, njira zatsopano zikapangidwa kuti athane ndi vuto la matenda ashuga.

Chifukwa chake, olemba adasinthitsa mapuloteni a glut2 a glucose transporter cDNA kale amasinthidwa ndi ma insulin cDNA okwanira a inshuwaransi ya HEP G2.

M'mapulogalamu a HEP G2 Insgl omwe amapezeka, shuga amayamba pafupi ndi zachilengedwe za insulin komanso amatha kuyankha mwachinsinsi pazinthu zina zobisika.

Ma microscopy a Immunoelectron adavumbulutsa ma grulin omwe amakhala ndi ma protein m'makhalidwe ofanana ndi granules omwe amapezeka mu mab-cell a zilumba za Langerhans. Kuthekera kwa kugwiritsa ntchito "cell b-cell" yopezeka ndi njira zopangira ma genetic zochizira matenda a shuga 1 kukukambidwa kwambiri.

Kuphatikiza pa kuthana ndi mavuto othandiza, mapangidwe a zochita za insulin, komanso maubwenzi ndi magwiridwe antchito a molekyulu, amaphunzira. Njira imodzi yofufuzira ndikumapangira zinthu zosiyanasiyana zochokera ku insulin ndi kuwunika kwawo kwazomwe zimayambitsa 23, 24.

Monga tafotokozera pamwambapa, njira zingapo zopangira insulin zimachokera pakupeza timadzi tating'onoting'ono tomwe timapangidwira (proinsulin), kenaka motsatiridwa ndi enzymatic cleavage kwa insulin ndi C-peptide. Pakadali pano, kupezeka kwa ntchito yachilengedwe kwawonetsedwa chifukwa cha C-peptide, zomwe zimapangitsa kuti azigwiritsa ntchito pochiritsa pamodzi ndi insulin.

Munkhani zotsatirazi, za C-peptide, komanso njira za kukonzekera kwake, zilingaliridwa.

Biotechnology popanga mankhwala

Chosangalatsa ndichomwe mukupeza mtundu wa 20K wa STGh. Ntchito yolimbikitsa ndikupeza komanso kuphunzira mitundu yosiyanasiyana ya STH, komanso STH yolumikizira mphamvu kuti ipangitse kuchuluka kwa mahomoni. Njira yoyambira idapangidwira kuti ipeze STHch yosavomerezeka ndi kanthu yayitali.

Kufanana ndi kupanga kwa STH, umisiri woyambirira wophatikizika wa kupanga mahomoni a adenohypophysis, kuphatikiza mitundu yonse yamitundu mitundu, ndi zina mwa zosintha kuchokera ku GST, zidapangidwa. Chofunika kwambiri ndikukhazikitsa pulogalamu yomwe ikuyang'aniridwa kuti ipange mankhwala othandizira STH (somatogen), opezeka ndi mainjiniering.

Zochitika pachipatala zawonetsa kuti, ndikukwaniritsa chithandizo chododometsa, ndikofunika kuti pakhale zida zambiri zamankhwala zokonzekera zopangidwa ndi maukadaulo osiyanasiyana kapenanso njira (MF, Ausomatin, Somatogen).

Chithandizo cha nthawi yayitali (kwa zaka) ndikakonzedwa kamodzi kwa HSCH kumapangitsa kuchepa kwa chidwi chake mkati mwake.

Mwapang'onopang'ono, izi zitha kukhala chifukwa cha kupangika kwa ma antibodies, koma chifukwa chachikulu chiyenera kufunidwa pamlingo wa ma receptors ndikuwongolera mahomoni.

Gwirani ntchito ndi GST, komanso kufufuza kwathunthu kwamahomoni obisika komanso mitundu yawo yambiri imapangitsa kuti athe kuphunzira machitidwe omwe adapangidwa ndi chilengedwe ndikuwamvetsa bwino. Kupezeka kwa mitundu yosiyanasiyana ya mbadwa za STH m'thupi kumawonetsa kuthekera ndi kugwiritsidwa ntchito kwawo, mwachitsanzo, kuchipatala.

Kupanga kukonzekera kwatsopano kwa STHch, ndikofunikira poyamba kuyang'ana zamitundu yachilengedwe ya mahomoni ndipo, ngati kuli koyenera, kuzikulitsa pogwiritsa ntchito genetic engineering, monga zimachitidwira ndi STHch monomer.

Pakupanga kukonzekera kwa STHch kuchokera ku GST, ukadaulo wathunthu wamafakitale wopanga mahomoni ena a adenohypophysis (LGH, FSHch, TTGch ndi ena) umakwaniritsidwa. Ndikofunikira kupititsa patsogolo kupanga mwakuwonetsa njira zatsopano zapamwamba (kufananirana ndi chromatography, ndi zina).

,, Landirani mahomoni oyera kwambiri pogwiritsa ntchito njira zophatikizika.

Ndikofunikira kukulitsa kupanga ndi kugwiritsa ntchito magwiritsidwe a immunomicroanalysis a mahomoni a adenohypophysis kuti apezeke ngati ali ndi sayansi, kuti akwaniritse kupanga koyenera kwa ma antibodies oyimira osiyanasiyana pamiyeso yosiyanasiyana, kuti apange kukonzekera kwatsopano kwa STHch, kuphatikiza omwe sangathe kugwira ntchito.

Zakuti STH imakhudza mapuloteni, mafuta, komanso michere metabolism, imagwira ntchito pamalo opanda cell, ndipo ndi anabolic, imapereka chiyembekezo chachikulu chogwiritsidwa ntchito yake kuti ipangitse njira kukonza komanso kuchiza matenda osiyanasiyana. Kafukufuku wambiri pazinthu izi, komanso mwayi wogwiritsa ntchito mitundu yosinthidwa ndi mitundu yosiyanasiyana ya STGch, ndi ntchito yofunikira komanso yolimbikitsa.

Kupeza insulin mu biotechnology

Insulin, mahomoni a peptide a zisumbu za Langerhans za kapamba, ndiye chithandizo chachikulu cha matenda ashuga. Matendawa amayamba chifukwa cha kuchepa kwa insulin ndipo amawonetsedwa ndi kuchuluka kwa shuga m'magazi. Mpaka posachedwapa, insulini idapezeka kuchokera ku zikondamoyo za ng'ombe ndi nkhumba.

Mankhwalawa anali osiyana ndi insulin ya anthu chifukwa cha m'malo mwa 1-3 amino acid, kotero kuti panali vuto la kuyanjana, makamaka kwa ana. Kugwiritsidwa ntchito kwachilengedwe kwa insulin kunali kovuta chifukwa cha mtengo wake wokwera komanso zoperewera.

Mwa kusintha kwa mankhwala, insulin kuchokera ku nyama idapangidwa kuti ikhale yosiyana ndi anthu, koma izi zimatanthawuza kukwera kwina kwa mtengo wa chinthu.

Kuyambira 1982, EliLilly wakhala akupanga ma insulin okhala ndi ma genulin malinga ndi kapangidwe ka ma CD a E. coli A ndi B. Mtengo wa malonda watsika kwambiri, chifukwa insulin yake imakhala yofanana ndi anthu. Kuyambira 1980, pakhala pali malipoti pofalitsa nkhani zokhudza kuphatikizika kwa majini a proinsulin, omwe amayendera mahomoni omwe amasintha kukhala mawonekedwe okhwima omwe alibe proteinol ochepa.

Teknoloji ya Encapsulation imagwiritsidwanso ntchito pochiza matenda ashuga: maselo a kapamba mu kapisozi, omwe amayamba kamodzi mthupi la wodwalayo, amatulutsa insulini pachaka.

Kuphatikizidwa kwa genetics kwakhazikitsa ma follicle osangalatsa komanso othandizira ma luteinizing. Izi ma peptides amapangidwa ndi ma subunits awiri. Patsikuli ndipamalo opanga ma oligopeptide mahomoni a mantha am'mimba - enkephalins, omwe amapangidwa kuchokera kutsalira la 5 amino acid, ndi endorphins, analogues of morphine.

Mukagwiritsidwa ntchito moyenera, ma peptides amachepetsa ululu, amapanga kusintha kwamphamvu, kuwonjezera mphamvu, kuyang'ana chidwi, kukonza kukumbukira, ndikuyika kugona ndikugalamuka.

Mwachitsanzo pakugwiritsa ntchito njira zopangira majini ndi kapangidwe ka p-endorphin pogwiritsa ntchito ukadaulo wa mapuloteni wosakanizidwa womwe wafotokozedwa pamwambapa kwa mahomoni ena a peptide, somatostatin.

Njira zopangira insulin yaumunthu:

Pakalembedwe, njira yoyamba yopezera insulin chifukwa cha njira zochiritsira ndikudzipatula kwa chifaniziro cha timadzi timeneti kuchokera kuzinthu zachilengedwe (ma ispancreas a kapamba a ng'ombe ndi nkhumba).

Mu 20s ya zaka zapitazi, zidapezeka kuti ma insulini a bovine ndi nkhumba (omwe ali pafupi kwambiri ndi insulin ya anthu pakupanga ndi amino acid sequence) amawonetsa zochitika mthupi la munthu poyerekeza ndi insulin yaumunthu. Pambuyo pake, insulin kapena ng'ombe ya nkhumba imagwiritsidwa ntchito pochiza odwala omwe ali ndi matenda a shuga a mtundu woyamba.

Komabe, patapita kanthawi zidawonetsedwa kuti nthawi zina ma antibodies a bovine ndi porcine insulin ayamba kudzikundikira m'thupi la munthu, potero pokana mphamvu zawo.

Kumbali inayi, chimodzi mwazabwino za njira iyi yopezera insulini ndikupezeka kwa zinthu zopangira (bovine ndi nkhumba insulin zitha kupezeka mosavuta), zomwe zidagwira ntchito yofunika pakupanga njira yoyamba yopanga insulin yaumunthu.Njira imeneyi imatchedwa semi-synthetic.

Mwanjira yopanga insulin yaumunthu, insulin ya nkhumba idagwiritsidwa ntchito ngati chakudya. C-terminal octapeptide ya B unyolo inachotsedwa ku insulin yoyesedwa, pambuyo pake C-terminal octapeptide ya insulin yaumunthu inapangidwa.

Kenako adalumikizidwa ndi mankhwala, magulu oteteza amachotsedwa ndikutsuka insulin. Poyesa njira iyi yopezera insulini, kudziwa kwathunthu momwe timadzi timene timapezera timene timapangidwa ndi insulin ya anthu timawonetsedwa.

Choyipa chachikulu cha njirayi ndi kukwera mtengo kwa insulin yomwe ikubwera (ngakhale pano, kuphatikizidwa kwa mankhwala octapeptide ndizosangalatsa mtengo, makamaka pamsika wamafuta).

Pakadali pano, insulin yaumunthu imapezeka kwambiri m'njira ziwiri: kusintha kwa insulin ndi njira yopangira-enzymatic ndi njira yothandizira majini.

Poyambirira, njirayi idakhazikitsidwa chifukwa chakuti insulini ya nkhumba imasiyana ndi insulin ya anthu m'malo mwake pa C-terminus ya Ala30Thr B unyolo.

M'malo mwa alanine ndi threonine kumachitika ndi enzyme-othandizira cleavage wa alanine ndi kuwonjezera kwa otsalira a threonine otetezedwa ndi gulu la carboxyl, lomwe limapezeka kwambiri pakuwonjezera kosakaniza. Pambuyo pokhazikika kwa gulu loteteza O-tert-butyl, insulin yaumunthu imapezeka.

Insulin anali mapuloteni oyamba omwe amapezeka kuti amagulitsidwe pogwiritsa ntchito ukadaulo wa DNA. Pali njira ziwiri zazikulu zopangira insulin yaumunthu.

Poyambirira, zophatikiza (zopangira zosiyana) zimapezeka maunyolo onse awiri, ndikutsatira mwa kupukutika kwa molekyulu (mapangidwe a milatho yopanda tanthauzo) komanso kulekanitsa ma isoforms.

Mu chachiwiri, kupanga mu mawonekedwe a precursor (proinsulin) kenako enzymatic chimbudzi ndi trypsin ndi carboxypeptidase B kupita ku mtundu wogwira wa mahomoni.

Pakadali pano, ndikofunikira kwambiri kuti mupeze insulini mwanjira yoyambira, yomwe imatsimikizira kutsekeka koyenera kwa milatho yopanda malire (munthawi yakukonzekera maunyolo, zotsatizana zamagetsi, kusiyanitsa kwa isoforms ndikukonzanso kumachitika).

Ndi njira zonsezi, ndizotheka kuti aliyense payekhapayokha kupeza zoyambira (A- ndi B-unyolo kapena proinsulin), komanso ngati gawo la mapuloteni a haibridi. Kuphatikiza pa unyolo wa A ndi B kapena proinsulin, mapuloteni a haibridi akhoza kukhala ndi:

1) onyamula mapuloteni - poperekera mapuloteni osakanizidwa kumalo opangika a khungu kapena chikhalidwe,

2) gawo loyanjana - limathandizira kwambiri kudzipatula kwa mapuloteni osakanizidwa.

Potere, zonsezi zimatha kupezeka nthawi imodzi mu kapangidwe ka mapuloteni osakanizidwa. Kuphatikiza apo, popanga mapuloteni a haibridi, mfundo zamaulidwe ochulukirapo zitha kugwiritsidwa ntchito (ndiye kuti, mapepala angapo a polypeptide omwe amapezeka amapezeka mu mapuloteni osakanizidwa), omwe angakulitse kwambiri zipatso za chandamale.

Kulingalira kwa proinsulin m'maselo a E. coli ..

Strain JM 109 N1864 yokhala ndi proteinotide yotulutsa fusion, yomwe imakhala ndi proinsulin yokhala ndi puloteni A ya Staphylococcus aureus yomwe idalumikizidwa ndi N-terminus kudzera mwa zotsalira za methionine, idagwiritsidwa ntchito.

Kulima kwa saturated biomass yama cell a recombinant kupanikizana kumapereka chiyambi cha kupanga mapuloteni osakanizidwa, kudzipatula ndikusinthidwa komwe mu chubu kumabweretsa insulin.

Kuwona mapu ndi kuwunika kwakuwonekera kwa proinsulin yoyeretsedwa ndi ion kusinthana ndi chromatography pa anion exchange resin ndi RP (gawo losinthika) HPLC (kuchuluka kwa madzi amadzimadzi a chromatography) iwonetsa kukhalapo kwa milatho yopanda tanthauzo yogwirizanitsa milatho yama proinsulin achibadwa. Amanenanso pakupanga njira yatsopano, yosinthika yopangira insulin yaumunthu pakupanga ma genetic mainjini a prokaryotic. Olembawo adawona kuti insulini yomwe idapangidwa mu kapangidwe kake ndi zochita zake zimakhala zofanana ndi mahomoni opatulidwa ndi kapamba.

Posachedwa, chidwi chachikulu chaperekedwa kuti njira zosavuta zopangira insulin zithandizenso mwa kuyambitsa majini. Chifukwa chake, mapuloteni ophatikizika adapangidwa wopangira peptide ya interleukin yolumikizidwa ndi N-terminus ya proinsulin kudzera mwa zotsalira za lysine. Mapuloteni adawonetsedwa bwino ndikuwonetsedwa pamatupi ophatikizika.

Pambuyo podzipatula, mapuloteniwo adamugaya ndi trypsin kuti apange insulin ndi C-peptide. Gulu lina la ofufuza linachitanso chimodzimodzi. Mapuloteni ophatikizika okhala ndi proinsulin komanso magawo awiri opanga a staphylococcus Puloteni yomanga IgG idapangidwa pamatupi ophatikizidwa, koma inali ndi mawonekedwe apamwamba.

Mapuloteniwa adayesedwa ndi IgG othandizira chromatography ndikugayidwa ndi trypsin ndi carboxypeptidase B. The insulin ndi C-peptide yoyambitsa idatsukidwa ndi RP HPLC. Mukamapanga zida zopangidwa, kuchuluka kwa mapuloteni onyamula ndi polypeptide yoyambira ndikofunikira kwambiri.

Kupanga kwa mapangidwe a fusion kumafotokozedwa komwe protein yaumunthu ya seramu albin imagwiritsidwa ntchito ngati polypeptide. Amodzi, atatu ndi asanu ndi awiri a C-peptides adalumikizidwa nawo.

Kupeza proinsulin yosinthika, yomwe inali ndi malo a Arg32Tyr. Puloteniyu ataphatikizidwa ndi trypsin ndi carboxypeptidase B, insulin yachilengedwe komanso C-peptide yokhala ndi zotsalira za tyrosine zidapangidwa. Wotsirizirayi, atalemba zilembo za 125I, amagwiritsidwa ntchito mwachangu mu radioimmunoassay.

Chidwi chachikulu chimaperekedwanso kwa fluorescent insulin. Mu ntchitoyi, olemba adafufuza momwe ntchito ikuyendera ndi kuphunzitsika kwa njira za chromatographic pakuwunika kwa magawo onse amtundu wa insulin yopanga anthu ndipo adapanga ndandanda ya magwiridwe antchito a chromatographic kuti athe kudzipatula ndikuwonetsa zinthu zomwe zimadza.

Kuphatikiza apo, njira zikupangidwa kuti zizigwiritsa ntchito kuti zizigwiritsa ntchito moyenera komanso zimathandizira njira zodziwitsira kuyera ndi kuchuluka kwa insulini.

Kafukufuku wokhudzana ndi kugwiritsa ntchito RP yamadzimadzi chromatografia ndikuwunika kwa electrochemical kuti adziwe insulin akunenedwa, ndipo njira yodziwira insulini yokhayokha kuchokera ku Langerhans islet ndi immunoaffrist chromatography yodziwika ndi mawonekedwe a spectrometric yapangidwa.

Ntchitoyi, kuthekera kwa kugwiritsa ntchito mwachangu-kutsimikiza kwa insulini pogwiritsa ntchito capillary electrophoresis yodziwika ndi laser-fluorescence kunasanthulidwa.Kusanthula kumachitika powonjezera pa sampule kuchuluka kwa insulin yolembedwa ndi phenylisothiocyanate (FITC) ndi chidutswa cha Fab cha monoclonal insulin antibodies. Yolembedwa komanso yolimbitsa thupi nthawi zonse imachita nawo mpikisano wa Fab. FITZ-yokhala ndi insulini yokhala ndi insulin komanso zovuta zake ndi Fab zimalekanitsidwa m'masekondi 30.

Genetic engineering insulin

Funso lazomwe insulin imapangidwira ndilothandiza osati kwa madokotala ndi akatswiri a zamankhwala okha, komanso kwa odwala matenda a shuga, komanso abale awo ndi anzawo.

Masiku ano, mahomoni apadera ndi ofunika kwambiri paumoyo wa anthu amatha kupezeka kuchokera ku zopangira zosiyanasiyana pogwiritsa ntchito matekinoloje opangidwa mwapadera komanso oyesedwa mosamala. Kutengera njira yokonzekera, mitundu yotsatirayi ya insulin imasiyanitsidwa:

Nkhumba kapena bovine, wotchedwanso nyama
Nkhumba yosinthidwa yazinthu ziwiri zosinthidwa
Makina opangidwira kapena obwereza
Kusinthidwa Mtundu
Zopanga

Insulin ya nkhumba yagwiritsidwa ntchito kutalika kwambiri kwa matenda ashuga. Kugwiritsidwa ntchito kwake kunayambiranso zaka 20 zapitazo.

Dziwani kuti nkhumba kapena nyama ndiye chokhacho chokhacho mpaka 80s ya zaka zapitazi. Kuti mupeze, minofu ya zikondamoyo za nyama imagwiritsidwa ntchito.

Komabe, njirayi singatchulidwe kuti ndiyabwino kapena yosavuta: kugwira ntchito ndi zinthu zosaphika sikophweka nthawi zonse, ndipo zopangira palokha sizokwanira.

Kuphatikiza apo, kupezeka kwa insulin ya insulin sikugwirizana kwathunthu ndi kapangidwe ka timadzi tomwe timapangidwa ndi munthu wathanzi: zotsalira zingapo za amino acid zilipo mu kapangidwe kake. Dziwani kuti mahomoni opangidwa ndi kapamba amphaka ali ndi kusiyana kwakukulu kwambiri, komwe sikungatchulidwe chodabwitsa.

Pokonzekera izi, kuphatikiza pa zinthu zambiri zopanda michere, zomwe zimadziwika kuti proinsulin zimakhala ndi zinthu zosasinthika, chinthu chomwe sichingagawanikidwe pogwiritsa ntchito njira zamakono zodziyeretsera. Ndiye amene nthawi zambiri amakhala magwero a zovuta zina, zomwe zimakhala zowopsa kwambiri kwa ana ndi okalamba.

Mankhwala amafunanso ndalama kwa odwala matenda ashuga. Pali mankhwala anzeru amakono aku Europe, koma samangokhala chete. Izi ndi.

Pachifukwachi, asayansi padziko lonse lapansi akhala ndi chidwi chofuna kubweretsa momwe ma mahomoni opangidwa ndi nyama amagonjera kwathunthu mahomoni a pancreatic a munthu wathanzi. Kupambana kwenikweni mu pharmacology ndikuchiza matenda ashuga kunali kupanga mankhwala opangidwa ndi theka omwe amapezeka m'malo mwa amino acid alanine pokonza nyama ndi threonine.

Nthawi yomweyo, njira yopangira mahomoni ena imachokera pakukonzekera nyama. Mwanjira ina, amangosintha ndikukhala ofanana ndi mahomoni opangidwa ndi anthu. Zina mwa zabwino zawo ndikugwirizana ndi thupi la munthu komanso kusapezeka kwa zinthu zina zonse.

Zoyipa za njirayi zimaphatikizaponso kuperewera kwa zinthu zopanda pake ndi zovuta zogwira ntchito ndi zinthu zachilengedwe, komanso mtengo wokwera waukadaulo womwewo komanso mankhwala omwe amapezeka.

Motere, mankhwala abwino kwambiri ochizira matenda a shuga ndi omwe amapanganso insulin yomwe imapezeka ndi ma genetic engineering.

Zodabwitsa ndizakuti, nthawi zambiri zimatchedwa kuti insulin yopangidwa kuchokera ku chibadwa, motero zimawonetsera njira yopezera, ndipo chotsatira chake chimatchedwa insulin ya munthu, potero chikugogomezera kudziwikiratu kwake kwa mahomoni opangidwa ndi kapamba wa munthu wathanzi.

Mwa zabwino za genulin engineering insulin, munthu ayenera kuzindikira kuyera kwake kokwanira komanso kusowa kwa proinsulin, komanso kuti siyambitsa zomwe sizingachitike ndipo alibe zotsutsana.

Funso lomwe limafunsidwa pafupipafupi ndikomveka: kodi insulini yopangidwanso ndi iti? Ndikusintha kuti timadzi timeneti timapangidwa ndi yisiti tizilombo, komanso Escherichia coli, woyikidwa mu sing'anga wapadera wa michere. Kuphatikiza apo, kuchuluka kwa zinthu zomwe zapezeka ndizambiri kwambiri kotero kuti ndizotheka kusiya kugwiritsa ntchito mankhwala omwe amapezeka kuchokera ku ziwalo za nyama.

Zachidziwikire, izi sizokhudza a E. coli osavuta, koma za mtundu wosinthika komanso wokhoza kutulutsa insulin yaumunthu yopanga majini, kapangidwe ndi mawonekedwe ake omwe ali ofanana ndendende ndi mahomoni opangidwa ndi maselo a kapamba a munthu wathanzi.

Ubwino wa genetic engineering insulin sikufanana kwawo kofanana ndi mahomoni amunthu, komanso mwayi wokonzekera, kuchuluka kwakakwanira kwa zinthu zopangira komanso mtengo wotsika mtengo.

Asayansi kuzungulira padziko lonse lapansi akuti kupanga insulini yothandizanso kupindulitsa kwa matenda ashuga. Tanthauzo la zomwe apezazi ndizabwino kwambiri ndipo nkofunika kuti kuzidalira.

Ndizosavuta kuzindikira kuti lero pafupifupi 95% ya kufunika kwa timadzi timeneti imakwaniritsidwa mothandizidwa ndi insulin.

Nthawi yomweyo, anthu masauzande ambiri omwe kale anali ndi mankhwala osokoneza bongo adalandira mwayi wokhala ndi moyo wabwinobwino.

Ndinadwala matenda ashuga kwa zaka 31. Tsopano ali wathanzi. Koma, makapisozi awa ndi osatheka ndi anthu wamba, safuna kugulitsa mankhwala, sizopindulitsa kwa iwo.

Momwe insulin yolumikizira anthu imagwirira ntchito

Mankhwalawa amachokera ku mtundu woyamba wa matenda a shuga 1, umagwiritsa ntchito mitundu iwiri yama cell insulin. M'mafakisi, amagulitsidwa monga yankho ndipo ali ndi "Wokondedwa". Mtundu wachiwiri wa matenda amathanso kuthandizidwa ndi mankhwalawa ngati mankhwala omwe sanayenere kudwala matenda ashuga.

Insulin yopangidwa ndi chibadwa imagwiritsidwanso ntchito ngati munthu akudwala matenda a shuga. Madokotala nthawi zambiri amapereka ma jakisoni kwa amayi apakati omwe amapezeka ndi matenda osokoneza bongo pamene mapiritsi ochepetsa shuga komanso zakudya zochizira sizithandiza.

Mwambiri, ma insulin omwe amapanga ma genetically kapena ma GMO amagwiritsidwa ntchito pakubala, akamachitidwa opaleshoni, kapena ngati wodwalayo wavulala kwambiri. Mankhwala amakulolani kuti musinthe moyenera kugwiritsa ntchito mahomoni ochita zinthu mwachangu.

Musanagwiritse ntchito zomangira zamtundu wa insulin biphasic, ndikofunikira kuyesa ndikuwona ngati mankhwalawa ndi oyenera kwa wodwala. Ngati wodwala matenda ashuga aulula hypoglycemia, kugwiritsa ntchito mankhwalawa osavomerezeka.
Chiwembu chogwira ntchito yothetsera vutoli ndikuti ma insulin omwe amapangidwa ndi majini amayanjana ndi maselo, zomwe zimabweretsa mapangidwe. Maselo akalowa izi, amakondoweza ndikuyamba kugwira ntchito molimbika. Zotsatira zake, ma enzyme ochulukirapo amapangidwa.
Mukuchita izi, glucose amalowetsedwa mwachangu, michere yomwe imalowa m'thupi imakonzedwa mwachangu. Chifukwa chake, chiwindi chimapanga shuga yayitali, ndipo mapuloteni amatha kuyamwa mwachangu kwambiri.

Upangiri wokhudzana ndi mankhwalawa umatengera mlingo, mtundu wa insulin, kusankha kwa jekeseni. Njira iliyonse iyenera kuchitidwa pokhapokha povomerezana ndi adokotala. Jakisoni woyamba amachitika moyang'aniridwa ndi achipatala.

Malangizo ogwiritsira ntchito mankhwalawa

Monga kapena insulin biphasic umisiri wamtundu wa anthu ali ndi mayina osiyanasiyana ogulitsa. Komanso mahomoni amatha kusiyanasiyana nthawi yayitali, njira yokonzekera yankho. Zogulitsa zimatchulidwa kutengera mtundu wa insulin.

Ma insulin opangidwa ndi genetically ali m'gulu la mankhwala monga Humudar, Vozulim, Actrapid. Insuran, Gensulin. Uku si mndandanda wathunthu wa mankhwalawa, chiwerengero chawo chimakhala chachikulu.

Mankhwala onse omwe ali pamwambawa amasiyanasiyana malinga ndi kukhudzana ndi thupi.Ma GMO amatha kukhala maola angapo kapena kukhala otakataka masiku onse.

Mankhwala osakanikirana magawo awiri amaphatikiza mankhwala omwe amaphatikiza zinthu zina zomwe zimasintha nthawi yokumana ndi mankhwalawa.

Mankhwala oterewa amagulitsidwa mwanjira zosakanikirana, kuphatikiza mahomoni omwe amapezeka ndi chibadwa.
Ndalamazi zikuphatikizapo Mikstard, Insuman, Gansulin, Gensulin.
Mankhwala amagwiritsidwa ntchito kawiri pa tsiku, theka la ola musanadye. Dongosolo loterolo liyenera kutsatiridwa mosamalitsa, chifukwa mahomoni amakhudzana mwachindunji ndi nthawi yakudya.

Mwa kupanga jini la insulin yaumunthu, kukonzekera kumachitika komwe kumakhala ndi nthawi yodziwikiratu.

Njira yothetsera vutoli imayamba kugwira ntchito pasanathe mphindi 60, koma mphindi yayitali kwambiri.
Mankhwalawa amachotsedwa kwathunthu pambuyo pa maola 12.
Mankhwalawa ndi monga Insuran, Insuman, Protafan, Rinsulin, Biosulin.

Palinso ma GMO omwe amakhala ndi nthawi yochepa yowonekera. Izi zikuphatikizapo mankhwala a insulin Actrapid, Gansulin, Humulin, Insuran, Rinsulin, Bioinsulin. Ma insulini oterowo amakhala ndi gawo logwira ntchito patatha maola awiri kapena atatu, ndipo zizindikiritso zoyambirira za mankhwalawa zimatha kuwonekera pakatha theka la ola jakisoni.

Insulin isanaperekedwe, ma GMO amafunika kuwunika kuti adziwe ngati pali zinthu zina zakunja zamadzimadzi. Ngati zinthu zakunja, zotupa kapena mpweya zikuwoneka m'mankhwala, vial iyenera kutayidwa - mankhwalawo sioyenera kugwiritsidwa ntchito.

Insulin yomwe imagwiritsidwa ntchito iyenera kukhala yotentha kwambiri. Mlingo wa mahomoni uyenera kusinthidwa ngati wodwala matenda ashuga ali ndi matenda opatsirana, vuto la chithokomiro, matenda a Addison, hypopituitarism, komanso matenda a impso.

Kuukira kwa hypoglycemia ndikotheka ndi mankhwala osokoneza bongo, pakakhala kusintha kwa mtundu watsopano wa insulin, chifukwa chodumphira chakudya kapena kupsinjika thupi kwambiri. Vutoli limatha kukhala matenda omwe amachepetsa kufunikira kwa mahomoni - kuchuluka kwambiri kwa matenda a impso, matenda a chiwindi, kuchepa kwa chithokomiro, adrenal cortex, ndi pituitary gland.

Kutsika kowopsa kwa shuga m'magazi ndikotheka ndikusintha kwa jekeseni. Chifukwa chake, ndikofunikira kusintha kuchokera ku mtundu umodzi wa insulin moyenera pokhapokha ngati mukugwirizana ndi adokotala.
Ngati wodwala matenda ashuga amagwiritsa ntchito insulin yochepa, nthawi zina kuchuluka kwamafuta am'mimba amachepetsa pamalo a jakisoni kapena, matendawa amawonjezeka. Pofuna kupewa izi, jekeseni iyenera kuchitikira m'malo osiyanasiyana.

Amayi oyembekezera ayenera kudziwa kuti zofunika za insulini zimasiyana nthawi yayitali. Kuti muchite izi, muyenera kuchita mayeso a shuga wa tsiku ndi tsiku ndi glucometer.

Zochita za insulin pamthupi la munthu zikufotokozedwa mwatsatanetsatane mu kanema munkhaniyi.

1. kapangidwe ndi ntchito za insulin 5

1.1. Kapangidwe ka molekyulu 5

1.2. Kukula kwachilengedwe kwa insulin 7

1.3. Insulin Biosynthesis 8

2. genetic engineering insulin synthesis 10

2.1. Kugwiritsa ntchito njira zopangira ma genetic pakuphatikizidwa kwa mankhwala 10

2.2. Njira Zaukadaulo Zamtundu 11

2.3. Makina opanga insulin 14

Pomaliza 18

Zizindikiro zosokoneza bongo

Mukamagwiritsa ntchito insulin, ndikofunikira kutsatira malangizo a dokotala ndikuwonetsetsa kuchuluka kwa mankhwalawa.

Pakusagwirizana ndi malamulo komanso kumwa mopitirira muyeso, odwala matenda ashuga amayamba kupweteka kwambiri mutu, kukokana, njala, thukuta, kugunda kwamtima, munthu amakhala wokhazikika, wokwiyitsidwa. Zowawa m'thupi lonse komanso kunjenjemera zimawonedwanso.

Zizindikiro zoterezi ndizofanana kwambiri ndi chizindikiro cha kuchepa kwa shuga m'magazi.Ndi gawo locheperako lazizindikiro, wodwala matenda ashuga amatha kuthana ndi vutolo ndikulimbikitsa vutoli. Kuti muchite izi, idyani maswiti kapena chinthu chilichonse chomwe chili ndi shuga.

Ngati wodwala matenda ashuga apezeka, amagwiritsa ntchito njira ya dextrose, mankhwalawa amathandizidwa ndi odwala mpaka munthu atazindikira. Pazizindikiro zoyambirira zokayikitsa, ndikofunikira kuyimba ambulansi, yomwe idzaukitsa wodwalayo pogwiritsa ntchito njira zadzidzidzi.
Zotsatira zoyipa pambuyo pa kugwiritsidwa ntchito kwa ma GMO, munthu amakhala ndi totupa pakhungu la urticaria, ziwalo zam'mimba zimatupa, kuthamanga kwa magazi kumatsika kwambiri, kuyabwa komanso kupuma movutikira kumatha kuchitika. Uku ndikuchita koyipa kwa mankhwala, omwe patapita kanthawi amatha kudzimiririka okha osathandizira kuchipatala. Ngati vutoli lipitirirabe, muyenera kufunsa dokotala.
M'masiku oyamba kumwa insulin pokonzekera matenda ashuga, thupi nthawi zambiri limasowa madzi, munthu amakhala ndi vuto la kusowa kwamadzi, chikhumbo chake chimakulirakulira, kutupira m'manja ndi miyendo ndikuwoneka, ndipo kugona mosalekeza kumamveka. Zizindikiro zotere nthawi zambiri zimatha msanga ndipo sizibwerezanso.

Ndemanga ndi ndemanga

Ndili ndi matenda a shuga a 2 - osadalira insulin. Mnzake adalangiza kuti achepetse magazi ndi DiabeNot. Ndinalamula kudzera pa intaneti. Adayamba kulandira.

Ndimatsata zakudya zosasamala, m'mawa uliwonse ndidayamba kuyenda ma kilomita 2-3 ndikuyenda pansi. M'masabata awiri apitawa, ndazindikira kuchepa kwa shuga m'mamawa m'mawa asanadye chakudya cham'mawa kuyambira 9,3 mpaka 7.1, ndipo dzulo mpaka 6.

1! Ndikupitiliza njira yodzitetezera. Ndileka zolemba zabwino.

Margarita Pavlovna, inenso ndakhala ku Diabenot tsopano. SD 2. Ndilibe nthawi yodya komanso kuyenda, koma sindimagwiritsa ntchito maswiti ndi chakudya, ndimaganiza XE, koma chifukwa cha zaka, shuga akadali wamkulu.

Zotsatira zake sizabwino ngati zanu, koma kwa 7.0 shuga sizituluka sabata limodzi. Kodi mumapima shuga ndi glucometer iti? Kodi akukuwonetsani plasma kapena magazi athunthu? Ndikufuna kufananiza zotsatira ndikumwa mankhwalawo.

Zikomo kwambiri chifukwa chodzidziwitsa.

Makina opanga insulin

Kuti munthu akhale wathanzi, muyenera kuwunika kuchuluka kwa insulin mthupi. Hormone iyi iyenera kukhala yokwanira kuti glucose asadziunjike m'magazi. Kupanda kutero, vuto la metabolic, dokotala amazindikira matenda a shuga.

Njira zochizira matenda apamwamba a shuga ndizobwezeretsanso insulin, yomwe singapangidwe mwachilengedwe ndi thupi. Chifukwa chaichi, insulin yosungunuka imagwiritsidwa ntchito, yomwe ili yofanana ndi majini amtundu wa anthu. Kasitomala ndiye amachititsa kuti pakhale timadzi tambiri totere.

Popanga insulini, osati luso lokha kupanga mahomoni achilengedwe omwe amagwiritsidwa ntchito, opanga amagwiritsanso ntchito insulin yosinthika yopangidwa ndi anthu. Mankhwala okhala ndi "solubilis" amasonyezedwa ngati sungunuka.

Mitundu ya mankhwala

Ma insulin opangidwa ndi genetically ali m'gulu la mankhwala monga Humudar, Vozulim, Actrapid. Insuran, Gensulin. Uku si mndandanda wathunthu wa mankhwalawa, chiwerengero chawo chimakhala chachikulu.

Mankhwala onse omwe ali pamwambawa amasiyanasiyana malinga ndi kukhudzana ndi thupi. Ma GMO amatha kukhala maola angapo kapena kukhala otakataka masiku onse.

Mankhwala osakanikirana magawo awiri amaphatikiza mankhwala omwe amaphatikiza zinthu zina zomwe zimasintha nthawi yokumana ndi mankhwalawa.

Mankhwala oterewa amagulitsidwa mwanjira zosakanikirana, kuphatikiza mahomoni omwe amapezeka ndi chibadwa.
Ndalamazi zikuphatikizapo Mikstard, Insuman, Gansulin, Gensulin.
Mankhwala amagwiritsidwa ntchito kawiri pa tsiku, theka la ola musanadye. Dongosolo loterolo liyenera kutsatiridwa mosamalitsa, chifukwa mahomoni amakhudzana mwachindunji ndi nthawi yakudya.

Mwa kupanga jini la insulin yaumunthu, kukonzekera kumachitika komwe kumakhala ndi nthawi yodziwikiratu.

Njira yothetsera vutoli imayamba kugwira ntchito pasanathe mphindi 60, koma mphindi yayitali kwambiri.
Mankhwalawa amachotsedwa kwathunthu pambuyo pa maola 12.
Mankhwalawa ndi monga Insuran, Insuman, Protafan, Rinsulin, Biosulin.

Mankhwalawa amachotsedwa pakatha maola asanu ndi limodzi.

Kugwiritsa ntchito insulin sungunuka waumunthu wopangidwa chifukwa cha matenda ashuga

Insulin yopangidwa ndi chibadwa cha anthu ndi kusintha kwachilengedwe komwe kumachitika chifukwa cha insulin yomwe imatulutsa kapamba.

Osangokhala ma genetic a anthu osinthika mwanjira yomwe amagwiritsidwa ntchito kupangira, komanso zinthu zopangidwa mwapangidwe. Njira ina yodziwika yopangira mankhwalawa ndikugwiritsa ntchito insulin yosinthika, chifukwa

mu kapangidwe kake ndi ntchito zake, ili pafupi kwambiri ndi anthu.

Dongosolo la genetic engineering insulin kupanga.

Zizindikiro ndi contraindication

Insulin yopangidwa ndi chibadwa imatha kugwiritsidwa ntchito ngati mtundu 1 wa matenda a shuga komanso matenda a shuga 2, mukakhala kuti mankhwala osokoneza bongo omwe ali ndi vuto la hypoglycemic amawonedwa.

Itha kugwiritsidwa ntchito pamene wodwala ali ndi mitundu ina ya chikomokere. Ngati mayi woyembekezera wayamba kumene kukhala ndi matenda a shuga, ndiye kuti kugwiritsa ntchito insulin yaukadaulo kumaloledwa, koma pokhapokha zakudya sizithandiza kukhudzana ndi shuga. Kugwiritsidwa ntchito kwake kumalimbikitsidwa pothana ndi matenda omwe matenda oopsa amatha kuyang'aniridwa.

Kukonzekera kwa Gene kumayenda bwino pakubala kwawo, kuchitidwa, kuvulala, kusokonezeka kwa metabolic komanso kusintha kosintha pang'onopang'ono kupita ku insulin ndi nthawi yayitali.

Ndi koletsedwa kugwiritsa ntchito jini kukonzekera m'malo mwa mahomoni ndi hypersensitivity pazinthu zina za mankhwala ndi hypoglycemia.

Pharmacological zochita za mankhwala

Mankhwala osokoneza bongo amtunduwu amachitika ndi ma receptor of cell membrane, ndikupanga zovuta nawo. Ikalowa m'maselo, zovuta za mankhwalawa zimakhudza ntchito, ndikupangitsa kuti ikhale yogwira ntchito kwambiri ndikupanga michere yowonjezera.

Mlingo wa glucose umagwa chifukwa chakuti imakonzedwa mwachangu ndi maselo. Pambuyo pake, njira ya lipogenesis, kupanga mapuloteni kumathandizira kwambiri ndipo kuthamanga kwa chiwindi pakupanga glucose kumachepetsedwa.

Kutalika kwa mankhwalawa kudzatengera jakisoni, mtundu wa mankhwala, mlingo komanso kuyankha kwamunthu payekha. Ndi dokotala yekhayo amene angatulutse Mlingo ndi kupereka mankhwala ena mgululi. Munthawi yoyamba kumwa mankhwalawa, wodwalayo amayang'aniridwa kwambiri ndi madokotala kuti adziwe ngati mankhwalawo akana.

Zitsanzo za Mankhwala Otenga Majini a Genetically

Insulin yopangidwa ndi chibadwa cha anthu imapezeka m'mankhwala odziwika bwino monga Insuran, Insuman, Vozulim, Penfill, Biosulin, Gensulin, Actrapid, Rinsulin, Humulin, Humudar, Rosinsulin ndi ena onse.

Pali mitundu yosiyanasiyana ya insulin.Chimodzi mwazomwe zimagawidwa ndizokhudzana ndi nthawi ya mankhwalawa. Malinga ndi iye, insulin yosungunuka imatha kuchita pang'ono komanso yayitali. Muli mankhwala ophatikiza (biphasic insulin), omwe ali ndi chinthu chofunikira kwambiri komanso chokhalitsa.

Mankhwala amtunduwu amatchedwa osakaniza. Mwa iwo, pali omwe amapangidwa ndi kusintha kwa mahomoni amunthu. Ma insulin a magawo awiri ndi Mikstard, Gansulin, Insuman, Humulin ndi Gensulin. Afunika kugwiritsidwa ntchito kawiri pa tsiku, theka la ola musanadye.

Izi ndichifukwa choti insulini ya magawo awiri imakhala ndi chinthu chosakhalitsa, kudya komwe kumadalira chakudyacho.

Analogue ya uinjiniya yamadzi aanthu ili pakati pa mankhwala omwe amakhala ndi nthawi yayitali. Izi insulin yosungunuka imayamba kugwira ntchito patatha ola limodzi, ndipo kuchuluka kwake kwa ntchito kumachitika pambuyo pa maola 7. Pambuyo maola 12, amawonetsedwa. Mankhwala opangidwa ndi chibadwa cha anthu m'gululi ndi Insuman, Protafan, Humulin, Rinsulin, Biosulin, Gensulin, Gansulin, Insuran.

Pali mankhwala opangidwa ndi chibadwa cha anthu pakati pa gululi potsatira kanthawi kochepa. Mwachitsanzo, awa akuphatikizapo Gansulin, Insuran, Humulin, Rinsulin, Gensulin, Bioinsulin ndi Actrapid. Insulin yosungunuka yotere imayamba kugwira ntchito kwa theka la ola, ndipo ntchito yake imafika pamlingo wambiri maola angapo. Mankhwalawa amachotsedwa kwa maola 6.

Ngati mankhwala osokoneza bongo omwe ali ndi insulin yothandizidwa, kufooka, kugona, kutopa, kukwiya, kuzizira, thukuta lotupa, kunjenjemera, pallor, palpitations, mutu, kukokana ndi njala. Zonsezi ndi zizindikiro za hypoglycemia.

Ngati matendawa ayamba kumene ndipo ali m'magawo awo, magawo osavuta, ndiye kuti mutha kuchotsa Zizindikiro nokha. Kuti muchite izi, muyenera kudya zakudya zokhala ndi shuga komanso zamafuta ambiri, zomwe zimatha kudimbidwa mosavuta. Glucagon ndi dextrose solution amatha kuyambitsa thupi.

Ngati munthu wagwa, ndiye kuti muyenera kubaya jekeseni wa dextrose wosintha mpaka zinthu zitasintha.

Anthu ena atha kukhala ndi vuto losagwirizana ndi mankhwalawa omwe amapezeka ndi genulin. Zizindikiro zake zimatha kuphatikizira ming'oma, kutupa, kuchepa mphamvu, kuthamanga magazi, kufupika, kuthamanga, kutentha thupi, komanso kuyabwa.

Nthawi zina, hypoglycemia ndi chikomokere zimachitika. Mavuto ndi kudziwa kwa umunthu ngakhale kukomoka kumatha kuchitika. Wodwala akaphonya mankhwala, ndiye kuti akhoza kuyamba kukhala ndi hyperglycemia.

Ikuwoneka chifukwa cha Mlingo wochepa woyambirira, ndikupanga matenda opatsirana mthupi, komanso ngati simutsatira malamulo a zakudya.

Nthawi zina, wodwala amatha kukhala ndi lipodystrophy m'malo omwe mankhwalawo amaperekedwa.

Kumayambiriro kwa kugwiritsa ntchito mankhwalawa, kuzizira, kusowa kwa madzi, kugona, ndi chilakolako chofuna kudya zingachitike. Koma izi ndizakanthawi.

Kugwiritsira ntchito mankhwala achilengedwe a insulin monga mankhwala opangira majini ndi njira yabwino kwambiri yothandizira matenda ashuga.

Zimathandizira kuchepetsa kuchuluka kwa shuga chifukwa chakuti glucose amatengeka kwambiri ndi maselo, ndi machitidwe a kayendedwe kake. Koma mankhwalawa amafunika kugwiritsidwa ntchito mosamala malinga ndi zomwe dokotala wakupatsani, chifukwa

zimatha kuyambitsa mavuto osafunikira kwa wodwala.

Kodi insulin imapangidwa kuchokera ku chiyani?

Insulin ndiye mankhwala othandizira matenda a shuga a mtundu woyamba. Nthawi zina amagwiritsidwanso ntchito kukhazika mtima pansi wodwalayo ndikuwongolera moyo wake wamtundu wachiwiri wa matenda. Izi ndi chilengedwe chake ndi mahomoni omwe amatha kuthana ndi kagayidwe kazachilengedwe mu milingo yaying'ono.

Nthawi zambiri, kapamba amapanga insulin yokwanira, yomwe imathandizira kukhala ndi shuga m'thupi. Koma ndi zovuta zazikulu za endocrine, mwayi wokhawo wothandiza wodwala nthawi zambiri ndi jakisoni wa insulin kwenikweni.

Tsoka ilo, ndizosatheka kuzipeza pakamwa (mwanjira yamapiritsi), popeza zimawonongeka kwathunthu m'mimba ndikugaya mtengo wake wachilengedwe.

Zokonzekera zomwe zimapezeka kuchokera ku zopangira zachilengedwe

Kulandila timadzi ta nkhanu ndi ng'ombe ndi ukadaulo wakale womwe sugwiritsidwa ntchito masiku ano.

Izi zimachitika chifukwa cha mankhwala ochepa omwe adalandiridwa, zomwe zimapangitsa kuti pakhale zovuta zina komanso kuyeretsa kosakwanira.

Chowonadi ndi chakuti popeza mahomoni ali ndi mapuloteni, amakhala ndi ma amino acid ena.

Insulin yomwe imapangidwa mthupi la nkhumba imasiyana mu ma amino acid omwe amapangidwa ndi insulin yaumunthu 1 amino acid, ndi bovine insulin ndi 3.

Kumayambiriro ndi pakati pa zaka za zana la 20, pamene mankhwala ofananawo analibe, ngakhale insulin yotereyi inali yopambana pamankhwala ndikulola kutenga chithandizo cha odwala matenda ashuga kupita nawo kumalo ena atsopano. Ma Horoni omwe adapangidwa ndi njirayi amachepetsa shuga m'magazi, komabe, nthawi zambiri ankayambitsa zovuta komanso chifuwa.

Kusiyana pakapangidwe ka amino acid ndi zosafunikira zakumwa zimakhudza mkhalidwe wa odwala, makamaka m'magulu omwe ali pachiwopsezo cha odwala (ana ndi okalamba).

Chifukwa china chosalolera bwino insulin yotereyi ndi kupezeka kwa kuyamwa kwa mankhwala osagwiritsa ntchito (proinsulin), komwe sikunali kotheka kuti athetse kusiyanasiyana kwa mankhwalawa.

Masiku ano, pali ma insuge apamwamba apamwamba omwe alibe zoperewera. Zimapezeka kuchokera kapamba wa nkhumba, koma zitatha zimayatsidwa ndikuwonjezera kuyeretsa. Zili ndi mitundu yambiri ndipo zimakhala ndi zotuluka.

Insulin ya nkhumba yosinthidwa sikuti imasiyana ndi mahomoni amunthu, chifukwa chake imagwiritsidwabe ntchito

Mankhwalawa amaloledwa ndi odwala bwino ndipo samayambitsa mavuto, samachepetsa chitetezo cha mthupi ndipo amachepetsa shuga la magazi. Bovine insulin sikugwiritsidwa ntchito ngati mankhwala masiku ano, chifukwa chifukwa chakunja kwake kumakhudza chitetezo chathupi komanso machitidwe ena a thupi.

Katswiri wa Majini a Insulin

Insulin yaumunthu, yomwe imagwiritsidwa ntchito ngati odwala matenda ashuga, pamsika wamafuta amapezeka m'njira ziwiri:

Zosungidwa za insulin

ntchito enzymatic mankhwala a porcine insulin,
kugwiritsa ntchito majini osinthika amtundu wa Escherichia coli kapena yisiti.

Ndi kusintha kwa mankhwala a physico-cell, mamolekyulu a porcine insulin pansi pa michere yapadera amakhala ofanana ndi insulin yaumunthu. Kapangidwe ka amino acid kamakonzedwe kotsatira sikusiyana ndi kapangidwe kazinthu zachilengedwe zomwe zimapangidwa m'thupi la munthu.

Pakupanga, mankhwalawa amatsukidwa kwambiri, chifukwa chake sizoyambitsa thupi kapena mawonekedwe ena osayenera.

Koma nthawi zambiri, insulin imapezeka pogwiritsa ntchito mitundu yosinthika (genetically modified). Pogwiritsa ntchito njira za biotechnological, mabakiteriya kapena yisiti amasinthidwa m'njira yoti iwonso atulutse insulin.

Kuphatikiza pakupanga insulin yokha, kuyeretsedwa kwake kumachita mbali yofunika. Kuti mankhwalawa asayambitse zovuta zilizonse komanso zotupa, pagawo lililonse ndikofunikira kuyang'anira kuyera kwa zovuta za michere ndi zothetsera zonse, komanso zosakaniza zomwe zimagwiritsidwa ntchito.

Pali njira ziwiri zopangira insulin. Yoyamba mwa izo idakhazikitsidwa ndikugwiritsa ntchito mitundu iwiri yosiyanasiyana.

Iliyonse imapangika gawo limodzi lokha la mamolekyule a ma DNA (pali awiri okha, ndipo amapindika molunjika).

Kenako maunyolo awa amalumikizidwa, ndipo mu njira yotsatila ndikothekanso kupatulira mitundu yogwira insulin kwa iwo omwe alibe phindu lililonse kwachilengedwe.

Njira yachiwiri yomwe mungalandire mankhwalawa pogwiritsa ntchito Escherichia coli kapena yisiti zimatengera kuti microbe yoyamba imapanga insulin (ndiye kuti, omwe adalowetsa kale, proinsulin). Kenako, pogwiritsa ntchito enzymatic chithandizo, fomu iyi imayatsidwa ndikugwiritsidwa ntchito ngati mankhwala.

Ogwira ntchito omwe ali ndi mwayi wopezeka m'malo ena opanga zovala ayenera kuvala suti yodzitetezera, yomwe imachotsa kulumikizana ndi mankhwalawa ndi madzi amthupi la anthu.

Njira zonsezi nthawi zambiri zimakhala zamagalimoto, mpweya ndi mawonekedwe onse polumikizana ndi ma ampoules ndi mbale sizowoneka bwino, ndipo mizere yokhala ndi zida ndiyosindikiza.

Njira za biotechnology zimathandizira asayansi kuti aganizire njira zina zothanirana ndi shuga.

Mwachitsanzo, pakadali pano, maphunziro oyamba opanga ma cell a pancreatic beta akuchitika, omwe amatha kupezeka pogwiritsa ntchito njira zopangira majini.

Mwina m'tsogolomu adzagwiritsidwa ntchito kukonza zomwe zimachitika m'thupi mwa wodwala.

Kupanga kwamankhwala amakono a insulin ndi njira yovuta yaukadaulo yomwe imaphatikizapo magalimoto ndi kulowererapo pang'ono kwa anthu

Zowonjezera zina

Kupanga kwa insulin popanda maipi mu masiku amakono kuli kosatheka kulingalira, chifukwa amatha kusintha zinthu zake zamankhwala, kuwonjezera nthawi yanthawi ndikukwaniritsa kuyera kambiri.

Mwa zomwe ali nazo, zosakaniza zina zonse zitha kugawidwa m'magulu otsatirawa:

prolongators (zinthu zomwe zimagwiritsidwa ntchito popereka nthawi yayitali ya mankhwala),
mankhwala ophera tizilombo toyambitsa matenda
olimbitsa, chifukwa chomwe acidity yoyenera imasungidwa mu yankho la mankhwalawa.

Kupitiliza Zowonjezera

Pali ma insulin omwe amagwira ntchito kwa nthawi yayitali omwe zochita zake zimakhala kwa maola 8 mpaka 42 (kutengera gulu la mankhwalawo). Izi zimatheka chifukwa cha kuwonjezera pa zinthu zapadera - zotambuzira ku yankho la jakisoni. Nthawi zambiri, imodzi mwamafuta awa imagwiritsidwa ntchito pazolinga izi:

Mapuloteni omwe amalimbitsa nthawi ya mankhwalawa amayeretsedwa mwatsatanetsatane ndipo amakhala otsika pang'ono (mwachitsanzo, protamine). Mchere wamchere wa zinc sukhudzanso zochita za insulin kapena thanzi la munthu.

Tizilombo toyambitsa matenda tomwe timapangira insulini ndikofunikira kuti tizilombo tating'onoting'ono tisachulukane panthawi yosungirako ndikugwiritsa ntchito momwemo. Zinthu izi ndizosungirako komanso kuonetsetsa kuti mankhwalawo amasungidwa.

Kuphatikiza apo, ngati wodwala amapereka mahandawo kuchokera kwa iye yekha, ndiye kuti mankhwalawo amatha kwa masiku angapo.

Chifukwa cha ma antibacterial apamwamba kwambiri, sangakhale ndi mwayi wotaya mankhwala osagwiritsidwa ntchito chifukwa choganiza kuti zitha kubereka mwanjira yankho la ma virus.

Zinthu zotsatirazi zitha kugwiritsidwa ntchito ngati mankhwala ophera majeremusi popanga insulin:

Ngati yankho lake lili ndi ayoni a zinc, amakhalanso ngati chosungirako chifukwa cha antimicrobial

Popanga mtundu uliwonse wa insulini, zinthu zina zoyambitsa matenda zimakhala zoyenera. Kuchita kwawo ndi mahomoni kuyenera kufufuzidwa pamlingo woyeserera koyambirira, popeza osungirako sayenera kusokoneza zochita za insulin kapena kusokoneza katundu wake.

Kugwiritsira ntchito mankhwala osungirako nthawi zambiri kumapangitsa kuti timadzi timadzi timene timatulutsa pakhungu popanda kulandira mankhwala asanachitike ndi mowa kapena antiseptics (wopanga nthawi zambiri amatanthauza izi pamalangizo).

Izi zimathandizira kukhazikitsa kwa mankhwalawa ndikuchepetsa kuchuluka kwa mankhwalawa pokonzekera jakisoni wokha.

Koma malingaliro awa amangogwira ntchito ngati yankho limaperekedwa pogwiritsa ntchito syringe imodzi ya insulini ndi singano yopyapyala.

Olimbitsa

Olimba amafunika kuti pH yothetsera vutoli ikhalebe yokhazikika. Kusungidwa kwa mankhwalawa, ntchito zake ndi kukhazikika kwa katundu wamafuta zimadalira kuchuluka kwa acidity. Popanga mahomoni a jakisoni kwa odwala matenda ashuga, ma phosphates nthawi zambiri amagwiritsidwa ntchito pazolinga izi.

Kwa insulin yokhala ndi zinc, njira zothetsera kukhazikika sizofunikira nthawi zonse, chifukwa zitsulo zazitsulo zimathandizira kukhalabe koyenera.

Ngati agwiritsidwa ntchito, ndiye kuti mitundu ina ya mankhwala imagwiritsidwa ntchito m'malo mwa phosphates, popeza kuphatikiza kwa zinthu izi kumabweretsa kupendekera ndi kusafunika kwa mankhwalawo.

Chuma chofunikira chomwe chikuwonetsedwa kwa okhazikika onse ndi chitetezo ndi kulephera kulowa pazosintha zilizonse ndi insulin.

A endocrinologist wokhoza bwino ayenera kuthana ndi kusankha kwa majakisoni obwera ndi shuga kwa wodwala aliyense payekhapayekha.

Ntchito ya insulin sikuti kungokhala ndi shuga wambiri m'magazi, komanso osati kuvulaza ziwalo zina ndi machitidwe ena. Mankhwalawa ayenera kukhala osalowerera m'thupi, otsika pang'ono komanso oyenera kugula.

Ndiwothekanso kosavuta ngati insulin yosankhidwa ikhoza kusakanizidwa ndi mitundu yake ina kutengera nthawi yochitapo kanthu.