Zotsatira zoyipa za Insulin Therapy

Insulin ndi mahomoni a peptide omwe amapangidwa muzilumba za Langerhans za kapamba. Kutulutsidwa kwa mahomoni m'thupi la munthu kumagwirizana kwambiri ndi kuchuluka kwa shuga m'magazi, ngakhale kuti pali zinthu zina zingapo zomwe zimathandizanso pamagululi, kuphatikiza zochitika za mahomoni am'mimba kapamba komanso mahomoni am'mimba, amino acid, mafuta acids ndi matupi a ketone. Udindo waukulu wa insulin ndikupititsa patsogolo kugwiritsa ntchito kwachulukidwe komanso kusungidwa kwa ma amino acid, glucose ndi mafuta acid, ndikuletsa kuwonongeka kwa glycogen, mapuloteni ndi mafuta. Insulin imathandizira kuyendetsa shuga m'magazi, ndichifukwa chake zinthu za insulin nthawi zambiri zimalembedwa kwa odwala omwe ali ndi matenda a shuga, matenda a metabolism omwe amakhala ndi hyperglycemia (shuga yayikulu yamagazi). M'matumbo a minofu yolimba, mahomoni awa amakhala ngati anabolic komanso anti-catabolic, ndichifukwa chake insulin ya mankhwala imagwiritsidwa ntchito mu masewera othamanga komanso masewera olimbitsa thupi. Insulin ndi mahomoni omwe amatulutsidwa kuchokera ku kapamba m'thupi ndipo amadziwika ngati njira yokhazikitsira kagayidwe kazachilengedwe. Imagwira limodzi ndi mlongo wake, glucagon, komanso mahomoni ena ambiri kuti athe kuwongolera kuchuluka kwa shuga m'thupi ndi kuteteza motsutsana ndi kuchuluka kwa shuga (hyperglycemia) kapena shuga wochepa kwambiri (hypoglycemia). Nthawi zambiri, ndi mahomoni a anabolic, zomwe zikutanthauza kuti amathandizira pakupanga mamolekyulu ndi minyewa. Ili ndi magawo ena a mphamvu za catabolic (catabolism ndi njira yopangidwira ntchito yokhazikitsidwa ndi kuwonongedwa kwa mamolekyulu ndi minofu kuti apange mphamvu). Ngati yogwira, insulin ndi mapuloteni omwe amawagwiritsa ntchito amatha kuwonetseredwa pokhala ndi zotsatira ziwiri zazikulu:

Kuchuluka kwa kuyankha kwa chakudya. Zakudya zomanga thupi ndi mapuloteni ochepa otchulidwa ndizodziwika kwambiri. Mosiyana ndi mahomoni ambiri, insulini imakhala yotchuka kwambiri ndi chakudya komanso moyo, imagwiritsa ntchito kuchuluka kwa insulin kudzera mu chakudya komanso njira ya moyo. Ndikofunikira kuti mupulumuke, motero, mitu yomwe insulin siyipangidwe kapena yokhala ndi zochepa, ndikofunikira kuyilowetsa (mtundu I wa shuga). Insulin imakhala ndi vuto lotchedwa "insulin sensitivity," yomwe nthawi zambiri imatha kufotokozedwa kuti "kuchuluka kwa molekyulu imodzi ya insulin yomwe imatha kupereka mkati mwa cell." Mukakhala ndi chidwi kwambiri ndi insulin, mumachepetsa kuchuluka kwa insulini yomwe imafunikira kuchita zomwezo. Kukula kwakukulu ndi kutalika kwa insulin kumawonekera mu mtundu II wa matenda ashuga (mwa matenda ena achilendo). Insulin siyabwino kapena yabwino pankhani ya thanzi ndi kapangidwe ka thupi. Ili ndi gawo linalake mthupi ndipo kutsegulira kwake kungakhale kothandiza kapena ayi kwa anthu pawokha, kungakhale kwachilendo kwa ena. Nthawi zambiri anthu onenepa komanso omwe amangokhala amawonetsa insulini yochepa, pomwe othamanga wamphamvu kapena akatswiri ochepa masewera amakonda kugwiritsa ntchito njira zowongolera chakudya.

Zambiri zamahomoni

mRNA imakhomedwa chifukwa cha polypeptide unyolo womwe umadziwika kuti prroinsulin, womwe umangolungidwa mwachangu mu insulin chifukwa cha kufanana kwa amino acid. 1) Insulin ndi mahomoni a peptide (mahomoni okhala ndi ma amino acid), omwe ali ndi maunyolo awiri, unyolo wa alpha wokhala ndi ma 21 amino acid ndi unyolo wa beta wokhala ndi kutalika kwa 30 amino acid. Amalumikizidwa ndi milatho ya sulfide pakati pa unyolo (A7-B7, A20-B19) komanso mu alfa unyolo (A6-A11), womwe umapereka maziko a hydrophobic. Mapuloteni apamwamba amenewa amatha kukhalamo okha ngati monomer, komanso palimodzi ndi ena ngati dimer ndi hexamer. 2) Mitundu ya insulini iyi imapangika ndipo imayamba kugwira ntchito pamene masinthidwe achisokonezo amachitika pomangirira ku insulin receptor.

Mu kapangidwe ka vivo, kuwola ndi malamulo

Insulin imapangidwa mu zikondamoyo, m'malo othandizira omwe amadziwika kuti "islets of Langerhans", omwe ali m'maselo a beta ndipo akuimira okhawo omwe amapanga insulin. Pambuyo kaphatikizidwe, insulin imatulutsidwa m'mwazi. Ntchito yake ikangomaliza, imawonongeka ndi insulin yowononga insulin (insulin), yomwe imafotokozedwa paliponse ndipo imachepa ndi zaka.

Jakisoni wothandizidwa ndi insulin

Kuti zitheke, omasulira omwe ali ofunikira pakasayinidwe kosonyezedwa akuwonetsedwa molimbika. Kukondoweza kwa insulin kumachitika kudzera mu insulin yolandirira kunja kwa insulin receptor (yomwe imapinda mu cell membrane, yomwe imapangika kunja ndi mkati), zomwe zimapangitsa kusintha (kovomerezedwa) kusintha komwe kumapangitsa tyrosine kinase mkati mwa receptor ndikuyambitsa phosphorylation yambiri. Mapulogalamu omwe amapangika mwachindunji mkati mwa insulin receptor amaphatikiza zigawo zinayi zosankhidwa (insulin receptor substrate, IRS, 1-4), komanso mapuloteni ena angapo omwe amadziwika kuti Gab1, Shc, Cbl, APD ndi SIRP. Phosphorylation ya oimira awa amachititsa kusintha mwa iwo, zomwe zimapangitsa kuti azikhala ndi chizimba chowonetsa pambuyo pake. PI3K (yoyesedwa ndi akatswiri a IRS1-4) nthawi zina imayesedwa ngati mkhalapakati wamkulu wachiwiri 3) ndipo imachita mwanjira ya phosphoinositides kuyambitsa mkhalapakati wotchedwa Akt, yemwe ntchito yake imagwirizana kwambiri ndi kayendedwe ka GLUT4. Kuletsa kwa PI3k ndi wortmannin kumathetseratu kutenga insulin-mediated glucose, yomwe imawonetsa kufunikira kwa njirayi. Kusuntha kwa GLUT4 (kuthekera kosamutsa shuga kulowa mu khungu) kumadalira kutsegula kwa PI3K (monga tafotokozera pamwambapa), komanso pamasewera a CAP / Cbl. Kutsegulira kwa vitro PI3K sikokwanira kufotokoza kuchuluka kwa insulin yomwe imapangitsa. Kutsegulira kwa mkhalapakati woyamba wa APS kumakopa CAP ndi c-Cbl ku insulin receptor, pomwe amapanga mtundu wocheperako (womangidwa pamodzi) kenako ndikusuntha kudzera pa lipid rafts ku GLUT4 vesicles, komwe amalimbikitsa mapuloteni omanga a GTP kumtunda kwa cell. 4) Kuti muwone m'maganizidwe pamwambapa, onani njira ya insulin Encyclopedia ya majini ndi genomes a Institute of Chemical Research ku Kyoto.

Zotsatira za kagayidwe kazakudya

Insulin ndiye woyambira kagayidwe kazigawo ka glucose wamagazi (yemwe amatchedwanso shuga). Amachita masewera olimbitsa thupi ndi mlongo wake, glucagon, kuti akhale ndi shuga wamagazi ambiri. Insulin ili ndi gawo lakuwonjezera ndi kuchepa kwa glucose m'magazi, mwachitsanzo pakuwonjezera kaphatikizidwe ka shuga m'magazi, mawonekedwe onsewo ndi anabolic (kupangika kwa minofu), makamaka yosiyana ndi zovuta za glucagon (kuwononga minofu).

Kuwongolera kaphatikizidwe ka shuga ndi kuphwanya

Glucose imatha kupanga magwero osagwiritsa ntchito shuga m'chiwindi ndi impso. Impso zimabwezeranso pafupifupi kuchuluka kwa glucose komwe amapanga, kuwonetsa kuti akhoza kudzilimbitsa. Ichi ndiye chifukwa chake chiwindi chimawerengedwa kuti ndi gawo lalikulu la gluconeogenesis (gluco = glucose, neo = chatsopano, genesis = chilengedwe, chilengedwe cha glucose watsopano). 5) Insulin imasungidwa ku kapamba poyankha kuwonjezeka kwa shuga wamagazi omwe apezeka ndi maselo a beta. Palinso masensa a neural omwe amatha kuchita mwachindunji chifukwa cha kapamba. Miyezi ya shuga m'magazi ikakwera, insulini (ndi zinthu zina) zimayambitsa (m'thupi lonse) kuchotsa kwa shuga m'magazi kupita m'chiwindi ndi minyewa ina (monga mafuta ndi minofu). Shuga imalowetsedwa ndikuchotsedwa ku chiwindi kudzera mu GLUT2, yodziyimira mokwanira machitidwe a mahomoni, ngakhale kukhalapo kwa kuchuluka kwa GLUT2 m'matumbo akulu. 6) Makamaka, kukoma kokoma kumatha kuwonjezera ntchito ya GLUT2 m'matumbo. Kukhazikitsidwa kwa shuga mu chiwindi kumachepetsa mapangidwe a shuga ndikuyamba kulimbikitsa mapangidwe a glycogen kudzera kwa hepatic glycogeneis (glyco = glycogen, genesis = chilengedwe, kupanga glycogen). 7)

Glucose amatengedwa ndi maselo

Insulin imagwira ntchito yopulumutsa shuga kuchokera m'magazi kupita ku minofu ndi mafupa am'madzi kudzera mwa chonyamula chotchedwa GLUT4. Pali ma "GLut" 6 m'thupi (1-7, pomwe 6 ndi pseudogen), koma GLUT4 imafotokozedwa kwambiri ndipo ndizofunikira minofu ndi adipose minofu, pomwe GLUT5 imayang'anira fructose. GLUT4 sionyamula pamtunda, koma imapezeka muzinthu zochepa mkati mwa selo. Ma vesicles awa amatha kupita kumtunda kwa cell (cytoplasmic membrane) mwina ndikulimbikitsa insulin ku receptor yake, kapena potulutsa calcium kuchokera ku sarcoplasmic reticulum (contraction minofu). 8) Monga tanena kale, kulumikizana kwambiri kwa PI3K activation (kudzera pa insulin sign transduction) ndi mpweya wa CAP / Cbl transmuction (pang'ono kudzera insulini) ndikofunikira kuti kutsegulika kwa GLUT4 ndi glucose kuchitike ndi minofu ndi mafupa am'magazi (komwe GLUT4 imatchulidwa kwambiri).

Zokhudza insulin komanso kukana insulini

Kukana kwa insulini kumawonedwa pakudya zakudya zamafuta kwambiri (nthawi zambiri 60% yazakudya zonse zopatsa mphamvu kapena zapamwamba), zomwe mwina zimachitika chifukwa cha kuyanjana kokhazikika ndi kapangidwe ka kapangidwe ka CAP / Cbl kofunikira pakuyenda kwa GLUT4, popeza insulin receptor phosphorylation siyothandiza, ndi phosphorylation a apakati a IRS sizikhudzidwa kwambiri. 9)

Kulimbitsa Thupi

Kugwiritsa ntchito insulini kukonza magwiridwe antchito ndi mawonekedwe a thupi ndichinthu chotsutsana, chifukwa timadzi timeneti timakhala tikulimbikitsa kuchuluka kwa michere m'maselo amafuta. Komabe, kudziunjikira uku kumatha kuwongoleredwa kwakukulu ndi wogwiritsa ntchito. Malamulo okhwima kwambiri ophunzitsira kulemera kwakukulu kuphatikiza chakudya chopanda mafuta ochulukirapo amatsimikizira kusungidwa kwa mapuloteni ndi shuga m'maselo a minofu (m'malo momasunga mafuta acids m'maselo a mafuta). Izi ndizofunikira makamaka munthawi ya kuphunzitsidwa, m'mene thupi limathandizira, komanso kumva kwa insulin m'mitsempha ya chigoba kumakulitsidwa kwambiri poyerekeza ndi nthawi yopuma.
Mukamamwa atangomaliza maphunziro, timadzi timene timalimbikitsa kukula komanso kuonekera msanga. Pambuyo pa kuyamba kwa mankhwala a insulin, kusintha kwa maonekedwe a minofu kumatha kuonedwa (minofu imayamba kuwoneka bwino, ndipo nthawi zina imakhala yotchuka kwambiri).
Chowonadi chakuti insulin sichimapezeka pakuyesa mkodzo chimapangitsa kuti ikhale yotchuka pakati pa akatswiri othamanga komanso akatswiri omanga thupi. Chonde dziwani kuti, ngakhale atapita patsogolo pakayezetsa kuti adziwe mankhwalawo, makamaka ngati tikulankhula za analogues, lero insulin yoyambirira imanenedwabe ngati mankhwala "otetezeka". Insulin nthawi zambiri imagwiritsidwa ntchito limodzi ndi mankhwala ena omwe ali "otetezeka" pakuwongolera kupangira ma doping, monga ma cell kukula kwa anthu, mankhwala a chithokomiro, ndi jekeseni wotsika wa testosterone, yomwe pamodzi ingakhudze kwambiri mawonekedwe ndi ntchito ya wogwiritsa ntchito, zomwe mwina sizingachitike mantha chifukwa chabwino mukamayang'ana mkodzo. Ogwiritsa ntchito omwe sachita kuyezetsa magazi nthawi zambiri amawona kuti insulin yolumikizana ndi anabolic / androgenic steroids amachita synergistically. Izi ndichifukwa choti AAS imathandizira dziko la anabolic kudzera m'njira zosiyanasiyana. Insulin bwino imayendetsa bwino kayendedwe ka michere kupita ku maselo a minofu ndikulepheretsa kuwonongeka kwa mapuloteni, ndipo ma anabolic steroids (mwa zina) amawonjezera kwambiri kuchuluka kwa mapuloteni.
Monga tanena kale, mu mankhwala, insulin nthawi zambiri imagwiritsidwa ntchito pochiza matenda osiyanasiyana a shuga (ngati thupi la munthu silingathe kutulutsa insulin pamlingo wokwanira (mtundu I wa shuga mellitus), kapena sangathe kuzindikira insulin m'malo omwe ali ndi mulingo winawake m'magazi (shuga) mtundu II matenda ashuga)). Mtundu wa odwala matenda ashuga, motero, amafunika kumwa insulini pafupipafupi, popeza mulibe kuchuluka kwa mahomoni m'thupi la anthu otere. Kuphatikiza pa kufunikira kwa chithandizo chanthawi zonse, odwala amafunikanso kuyang'anitsitsa kuchuluka kwa shuga wamagazi ndikuyang'anira kudya shuga. Popeza adasintha moyo wawo, kuchita zolimbitsa thupi mokhazikika ndikukhala ndi chakudya chamagulu, anthu omwe amadalira insulin akhoza kukhala moyo wabwino komanso wathanzi. Komabe, ngati sanapatsidwe, shuga imatha kukhala matenda akupha.

Insulin idapezeka koyamba ngati mankhwala mu 1920s. Kupezeka kwa insulin kumalumikizidwa ndi mayina a sing'anga waku Canada a Fred Bunting ndi katswiri wazolimbitsa thupi ku Canada a Charles Best, omwe adagwirizana kupanga mankhwala oyamba a insulin ngati njira yoyamba yolandirira matenda a shuga. Ntchito yawo imalimbikitsidwa ndi lingaliro loyambirira lomwe linafunsidwa ndi Bunting, yemwe, monga dokotala wachichepere, anali ndi kulimbika mtima kuti anganene kuti kuchotsedwako kwachangu kuchokera ku zikondamoyo za nyama, zomwe zingathandize kuwongolera shuga la magazi a anthu. Kuti azindikire lingaliro lake, adafunsa katswiri wazanyama wodziwika bwino padziko lonse J.J.R. McLeod ochokera ku Yunivesite ya Toronto. Macleod, poyamba sanachite chidwi ndi lingaliro losazolowereka (koma ayenera kuti anali wodabwitsidwa ndi kukhudzika kwa Bunting ndi kukhazikika kwake), adasankha awiri ophunzira kuti amuthandize pantchito yake. Kuti mudziwe yemwe adzagwire ntchito ndi Bunting, ophunzira amachita maere, ndipo chisankho chagwera pa Omaliza maphunziro abwino.
Pamodzi Bunting ndi Brest adasintha mbiri ya zamankhwala.
Kukonzekera koyamba kwa insulini komwe asayansi amatulutsa kumachokera ku mbulu wa peancreas yaiwisi. Komabe, panthawi inayake, kupezeka kwa nyama zogulira ma labotale kunatha, ndipo poyesera kupitilizabe kufufuza, asayansi angapo adayamba kufunafuna agalu osochera pazolinga zawo. Asayansiwo adazindikira kuti amatha kugwira ntchito ndi kapamba wa ng'ombe zophedwa ndi nkhumba, zomwe zimathandizira ntchito yawo (ndikupangitsa kuti ikhale yovomerezeka). Njira yoyamba yachipambano ya matenda a shuga ndi insulin anali mu Januware 1922. Mu Ogasiti chaka chimenecho, asayansi adakwanitsa kuyika gulu la odwala kuchipatala, kuphatikiza wazaka 15 wazaka Elizabeth Hughes, mwana wamkazi wa purezidenti wa a Charles Evans Hughes. Mu 1918, Elizabeti anapezeka ndi matenda ashuga, ndipo kulimbana kwake kochititsa chidwi kwa moyo kunalengezedwa padziko lonse lapansi.
Insulin idapulumutsa Elizabeth kuti asafe ndi njala, chifukwa nthawi imeneyo njira yokhayo yochepetsera kukula kwa matendawa inali yoletsa kalori. Chaka chotsatira, mu 1923, Banging ndi Macleod adalandira Mphotho Nobel chifukwa cha zomwe apeza. Posakhalitsa, mikangano imayamba kuti ndani kwenikweni amene analemba zakupezekazi, ndipo pomaliza, Bunting amagawana mphoto yake ndi Best, ndi Macleod - ndi JB Collip, yemwe ndi katswiri wothandizirana pakuchotsa ndi kuyeretsa insulini.
Chiyembekezo chazopanga insulin itatha, Bunting ndi gulu lake adayamba mgwirizano ndi Eli Lilly & Co Kuphatikiza kunapangitsa kuti pakhale kukonzekera kwa insulin yoyamba. Mankhwalawa adachita bwino mwachangu komanso modabwitsa, ndipo mu 1923, insulini idapeza mwayi wambiri wamalonda, chaka chomwecho chomwe Bunting ndi Macleod adalandira Mphotho ya Nobel. M'chaka chomwechi, wasayansi waku Danish August Krog adayambitsa Nordisk Insulinlaboratorium, akufunitsitsa kuti abweretse ukadaulo wopanga insulin ku Denmark kuti athandize mkazi wake yemwe ali ndi matenda ashuga. Kampaniyi, yomwe pambuyo pake yasintha dzina lake kukhala Novo Nordisk, imadzakhala wopanga insulin wachiwiri padziko lonse, pamodzi ndi Eli Lilly & Co
Mwa miyambo yamakono, kukonzekera insulin koyambirira sikunakhale kokwanira kokwanira. Nthawi zambiri anali ndi magawo 40 a insulin ya nyama pa millilita, mosiyana ndi kuchuluka kwa magawo zana omwe avomerezedwa lero. Mlingo waukulu womwe umafunikira mankhwalawa, omwe poyamba anali ndi vuto lochepa, sanali abwino kwambiri kwa odwala, ndipo zotsatira zoyipa m'malo opaka jekeseni zimapezeka nthawi zambiri. Kukonzekerako kunalinso ndi zosayenera zamapuloteni zomwe zimatha kuyambitsa mavuto omwe amagwiritsidwa ntchito ndi ogwiritsa ntchito. Ngakhale izi, mankhwalawa adapulumutsa miyoyo ya anthu osawerengeka omwe, atalandira matenda a shuga, adakaweruzidwa kuti aphedwe. Zaka zotsatila, Eli Lilly ndi Novo Nordisk adasinthiratu kuyera kwa malonda awo, koma sizinaphule kanthu patsogolo paukadaulo wopanga insulin mpaka pakati pa 1930s, pomwe kukonzekera koyamba kwa insulin kunayambika.
Mu mankhwala oyamba otere, protamine ndi zinc zimagwiritsidwa ntchito kuti achedwetse insulin mthupi, kukulitsa ntchito yokhotakhota ndi kuchepetsa kuchuluka kwa jakisoni ofunikira tsiku ndi tsiku. Mankhwalawa adatchedwa Protamine Zinc Insulin (PTsI). Zotsatira zake zidatenga maola 24-36. Pambuyo pa izi, pofika mu 1950, Neutral Protamine Hagedorn (NPH) Insulin, yemwe amadziwikanso kuti Isofan Insulin, adamasulidwa. Mankhwalawa anali ofanana kwambiri ndi insulin PCI, kupatula kuti ikhoza kukhala yosakanikirana ndi insulin yokhazikika popanda kusokoneza kutulutsa kwa insulin. Mwanjira ina, insulini wamba imatha kusakanikirana mu syringe yomweyo ndi insulin NPH, ndikupereka kumasulidwa kwa magawo awiri, komwe kumadziwika ndi zotsatira zoyambirira za insulin, komanso kuchita nthawi yayitali chifukwa cha NPH.
Mu 1951, insulin Lente adapezeka, kuphatikizapo mankhwalawo Semilente, Lente ndi Ultra-Lente.
Kuchuluka kwa zinc zomwe zimagwiritsidwa ntchito pokonzekera ndizosiyanasiyana munthawi iliyonse, zomwe zimatsimikizira kusinthika kwawo kwakukulu malinga ndi nthawi yayitali ya zochita ndi pharmacokinetics. Monga ma insulins am'mbuyomu, mankhwalawa adapangidwanso popanda kugwiritsa ntchito protamine. Posakhalitsa, madokotala ambiri amayamba kusinthanitsa odwala awo kuchokera ku Insulin NPH kupita ku Tape, yomwe imangofunika mlingo umodzi wamawa (ngakhale odwala ena adagwiritsabe ntchito Loses insulin yamadzulo kuti azitha kuyang'anira shuga m'magazi kwa maola 24). Kwa zaka 23 zotsatira, panalibe kusintha kwakukulu pakupanga matekinoloje atsopano ogwiritsira ntchito insulin.
Mu 1974, matekinoloje oyeretsa ma chromatographic adalola kupanga insulini yoyambira nyama yokhala ndi zotsika kwambiri (zosakwana 1 pmol / l zosafunikira zama protein).
Novo anali kampani yoyamba kupanga insulin yopanga monocomponent pogwiritsa ntchito ukadaulo uwu.
Eli Lilly adayambitsanso mtundu wake wa mankhwala omwe amatchedwa "Single Peak" Insulin, omwe amalumikizidwa ndi chiwonetsero chimodzi mu protein zomwe zimawonetsedwa pakupenda mankhwala. Kusintha kumeneku, ngakhale kunali kofunika, sikunatenge nthawi yayitali. Mu 1975, Ciba-Geigy adayambitsa kupanga insulin yoyamba (CGP 12831). Ndipo patatha zaka zitatu zokha, asayansi a Genentech adapanga insulini pogwiritsa ntchito mtundu wa E. coli E. coli bacterium, woyamba kupanga wa insulin wokhala ndi kufanana kwa amino acid ofanana ndi insulin yaumunthu (komabe, ma insulini a nyama amagwira ntchito bwino kwambiri mwa anthu, ngakhale mawonekedwe ake ali osiyana pang'ono) . U.S. FDA idavomereza mankhwala oyamba otere operekedwa ndi Humulin R (Wokhazikika) ndi Humulin NPH kuchokera kwa Eli Lilly & Co mu 1982. Dzina la Humulin ndi chidule cha mawu akuti "anthu" ndi "insulin."
Posakhalitsa, Novo ayambitsa insulin yopanga insulin Actrapid HM ndi Monotard HM.
Kwa zaka zingapo, FDA idavomereza zokonzekera zina zambiri za insulin, kuphatikiza mankhwala osiyanasiyana a biphasic omwe amaphatikiza mitundu yosiyanasiyana ya kudya mwachangu komanso pang'onopang'ono. Posachedwa, a FDA avomereza kuti Eli Lilly Humalog achite mofulumira insulin. Zowonjezera zina za insulin zikufufuzidwa, kuphatikiza Lantus ndi Apidra kuchokera ku Aventis, ndi Levemir ndi NovoRapid ochokera ku Novo Nordisk. Pali mitundu yambiri yosiyanasiyana ya mankhwala a insulin omwe amavomerezedwa ndikugulitsidwa ku USA ndi maiko ena, ndipo ndikofunikira kumvetsetsa kuti "insulin" ndi gulu lonse la mankhwala. Kalasi iyi ikhoza kupitilirabe kukula ngati mankhwala atsopano apangidwa kale ndikuyesedwa bwino. Masiku ano, anthu pafupifupi 55 miliyoni amagwiritsa ntchito insulini yovomerezeka kuti alamulire matenda awo a shuga, zomwe zimapangitsa gawo lino lamankhwala kukhala lofunika komanso lopindulitsa.

Mitundu ya insulin

Pali mitundu iwiri ya insulin yopanga mankhwala - nyama ndi maumboni opanga. Insulin yachinyama imasungidwa kuchokera ku zikondamoyo za nkhumba kapena ng'ombe (kapena zonse). Kukonzekera kwa insulin kopangidwa ndi nyama kumagwera m'magulu awiri: insulin "yodziwika" komanso "yoyeretsedwa", kutengera mtundu wa zinthu zoyera komanso zomwe zili zina. Mukamagwiritsa ntchito zinthu ngati izi, nthawi zonse pamakhala mwayi wochepa wokhala ndi khansa ya kapamba, chifukwa cha kupezeka kwa zodetsa pokonzekera.
Biosynt synthet, kapena kupanga, insulin imapangidwa pogwiritsa ntchito tekinoloje ya DNA, momwemonso imagwiritsidwa ntchito popanga mahomoni akukula. Zotsatira zake ndi timadzi tating'onoting'ono tokhala ndi ma polypeptide okhala ndi "Chingwe" chimodzi chokhala ndi ma amino acid 21 omwe amalumikizidwa ndi ma cell awiri osakanikirana ndi "B chain" yokhala ndi ma amino acid 30. Zotsatira zake zokhudzidwa, mankhwala amapangika popanda mapuloteni omwe amadetsa kapamba, yemwe amawonedwa nthawi zambiri akamamwa insulini yochokera ku nyama, mwapangidwe komanso kwachilengedwe ofanana ndi insulin ya pancreatic. Chifukwa cha kukhalapo kwa zosokoneza mu insulin ya nyama, komanso kuti kapangidwe kake (pang'ono kwambiri) kamasiyana ndi kapangidwe ka insulin yaumunthu, insulini yopanga zomwe pakalipano imapezeka pamsika wamankhwala. Zamoyo zamtundu wa insulin / mitundu yake yotchuka imadziwikanso kwambiri pakati pa othamanga.
Pali zinthu zingapo zopangira insulin zomwe zilipo, chilichonse chomwe chimakhala ndi mawonekedwe apadera pokhudzana ndi isanayambike, pachimake ndi nthawi yayitali, komanso kuchuluka kwa kuchuluka kwa mankhwalawa. Kusiyanaku kwamankhwala kumathandizira madokotala kuti asinthe mapulogalamu othandizira odwala omwe amadalira insulin omwe ali ndi matenda a shuga, komanso kuchepetsa kuchuluka kwa jakisoni tsiku ndi tsiku, kupatsa odwala mwayi wolimbikitsidwa kwambiri. Odwala ayenera kudziwa mawonekedwe onse a mankhwalawa musanagwiritse ntchito. Chifukwa cha kusiyana pakati pa mankhwala, kusintha mtundu wa insulin kupita ku wina kuyenera kuchitika mosamala kwambiri.

Kuchita zinthu mwachidule

Humalog ® (Insulin Lizpro) Humalog ® ndi chithunzi cha insulin yofupikitsa ya anthu, makamaka, inshuwalansi ya Lys (B28) Pro (B29), yomwe idapangidwa ndikusintha malo a amino acid pamalo a 28 ndi 29. Amawerengedwa ngati ofanana ndi insulin wamba unit to unit, komabe, ili ndi ntchito mwachangu. Mankhwalawa amayamba kuchita pafupifupi mphindi 15 pambuyo povomerezeka, ndipo mphamvu yake yambiri imatheka pambuyo pa mphindi 30-90. Kutalika konse kwa mankhwalawa ndi maola 3-5. Lispro insulin nthawi zambiri amagwiritsidwa ntchito ngati chowonjezera pochita ma insulin ndipo amatha kutengedwa asanadye kapena atangomaliza kudya kuti atsanzire insulin. Ochita masewera ambiri amakhulupirira kuti kufupika kwa insulin kumeneku kumapangitsa kuti ikhale mankhwala abwino kwambiri pamasewera, chifukwa ntchito yake kwambiri imangokhala gawo logwira ntchito pambuyo pogwira, lomwe limadziwika kuti limatha kuthana ndi michere.
Novolog ® (Insulin Aspart) ndi analogue yaifupi ya insulin yaumunthu, yomwe idapangidwa ndikusintha amino acid proline pamalo a B28 ndi aspartic acid. Kukhazikika kwa mankhwalawa kumawonedwa pafupifupi mphindi 15 pambuyo povomerezeka, ndipo mphamvu yakeyo imatheka pambuyo pa maola atatu ndi atatu. Kutalika konse kwa kuchitapo kanthu ndi maola 3-5. Lispro insulin nthawi zambiri amagwiritsidwa ntchito ngati chowonjezera pochita ma insulin ndipo amatha kutengedwa asanadye kapena atangomaliza kudya kuti atsanzire insulin. Ochita masewera ambiri amakhulupirira kuti kugwira ntchito kwawo kwakanthawi kumapangitsa kuti ikhale chida chofunikira pamasewera, popeza ntchito yake yayikulu imatha kuyang'ana gawo lapa-post-Workout, lomwe limadziwika ndi chiwopsezo cholandidwa ndi michere.
Humulin ® R "Wokhazikika" (Insulin Inj). Chizindikiro cha insulin yaumunthu. Nagulitsidwanso monga Humulin-S® (sungunuka). Chogulitsachi chimakhala ndi mafuta a zinc-insulin omwe amasungunuka mumadzi oyera. Palibe zowonjezera pazomwe zimapangitsa kuti pang'onopang'ono amasulidwe, ndiye chifukwa chake nthawi zambiri amatchedwa "insulin ya insulle ya munthu." Pambuyo pothandizidwa ndi subcutaneous, mankhwalawa amayamba kuchita pambuyo 20-30 mphindi, ndipo mphamvu yakeyo imatheka pambuyo pa maola 1-3. Kutalika konse kwa kuchitapo kanthu ndi maola 5-8. Humulin-S ndi Humalog ndi mitundu iwiri yotchuka kwambiri ya insulin pakati pa omanga thupi komanso othamanga.

Wapakatikati komanso wautali wochita insulini

Humulin ® N, NPH (Insulin Isofan). Kuyimitsidwa kwa makristasi a insulin ndi protamine ndi zinc kuti achedwetse kumasulidwa ndikufalikira. Isofan insulin imawonedwa ngati insulin yapakatikati. Kukhazikika kwa mankhwalawa kumawonedwa pafupifupi maola awiri pambuyo povomerezeka, ndikufikira pakatha maola 4 mpaka 10. Kutalika konse kochedwa kupitilira maola 14. Insulin yamtunduwu sikuti imagwiritsidwa ntchito nthawi zambiri pamasewera.
Humulin ® L Tape (kuyimitsidwa kwapakati kwa zinc kuyimitsidwa). Kuyimitsidwa kwa makristasi a insulin ndi zinc kuti achedwetse kumasulidwa ndikuwonjezera zochita zake. Humulin-L amadziwika kuti ndi insulin yapakatikati. Kukhazikika kwa mankhwalawa kumawonedwa pambuyo pafupifupi maola atatu, ndikufikira pakapita maola 6 mpaka 14.
Kutalika konse kwa mankhwalawa kupitilira maola 20.
Insulin yamtunduwu sikugwiritsidwa ntchito kwambiri pamasewera.

Humulin ® U Ultralente (Kuyima kwa Zida yayitali)

Kuyimitsidwa kwa makristasi a insulin ndi zinc kuti achedwetse kumasulidwa ndikuwonjezera zochita zake. Humulin-L amadziwika kuti ndi insulin yokhala nthawi yayitali. Kukhazikika kwa mankhwalawa kumawonedwa pafupifupi maola 6 mutatha kuperekedwa, ndikufikira pakapita maola 14-18. Kutalika konse kwa mankhwalawa ndi maola 18-24. Insulin yamtunduwu sikuti imagwiritsidwa ntchito nthawi zambiri pamasewera.
Lantus (insulin glargine). Kutalika kwa insulin yaumunthu. Mu insulin yamtunduwu, amino acid asparagine yomwe ili pa A21 ikusinthidwa ndi glycine, ndipo ma arginine awiri amawonjezeredwa ndi C-terminus ya insulin. Kukhazikika kwa chochitika cha mankhwalawa kumawonedwa pafupifupi maola awiri atatha kutsatiridwa, ndipo mankhwalawa amawonedwa ngati alibe chiwonetsero chachikulu (ali ndi ndondomeko yokhazikika yotulutsa nthawi yonse ya ntchito yake). Kutalika konse kwa mankhwalawa ndi maola 20 mpaka 24 pambuyo pakubaya jekeseni. Insulin yamtunduwu sikuti imagwiritsidwa ntchito nthawi zambiri pamasewera.

Biphasic Insulin

Humulin ® osakaniza. Izi ndi zinthu zosakanikirana za insulin yosungunuka mwachangu momwe mungayambire kuchitira insulin kwa nthawi yayitali kapena yapakati kuti mupereke mphamvu yayitali. Amawonetsedwa ndi kuchuluka kwa zosakaniza, nthawi zambiri 10/90, 20/80, 30/70, 40/60 ndi 50/50. Zosakaniza za insulin zomwe zimachitika mwachangu.

Chenjezo: Insulin Yogundika

Mitundu yodziwika bwino kwambiri ya insulin imamasulidwa pamakonzedwe a 100 IU ya mahomoni pa millilita. Amadziwika ku US ndi madera ena ambiri monga zopangira U-100. Kuphatikiza pa izi, palinso mitundu ina ya insulin yomwe ilipo kwa odwala omwe akufuna kuti apatsidwe Mlingo wapamwamba komanso njira zambiri zachuma kapena zosavuta kuposa mankhwala a U-100. Ku United States, mutha kupezanso zinthu zomwe zili mndende nthawi 5, ndiye kuti 500 IU pa millilita. Mankhwalawa amadziwika kuti ndi "U-500", ndipo amapezeka pokhapokha ngati amupatsa mankhwala. Zogulitsa zotere zimatha kukhala zowopsa kwambiri mukasinthanitsa ndi inshuwaransi ya U-100 popanda kusintha masinthidwe. Popeza kuchuluka kwathunthu kwa muyezo woyenera wa mankhwala (2-15 IU) ndi mankhwala omwe ali ndi chidwi chachikulu, pazifukwa zamasewera, mankhwala a U-100 amagwiritsidwa ntchito pokhapokha.

Hypoglycemia

Hypoglycemia ndiye zotsatira zoyipa kwambiri mukamagwiritsa ntchito insulin. Ili ndi matenda owopsa omwe amapezeka ngati kuchuluka kwa shuga m'magazi kutsika kwambiri. Izi ndizowopsa komanso zowopsa zomwe zimachitika chifukwa cha kugwiritsa ntchito mankhwala a insulin komanso osagwiritsidwa ntchito kuchipatala, ndipo ayenera kumwedwa mozama. Chifukwa chake, ndikofunikira kudziwa zizindikiro zonse za hypoglycemia.
Otsatirawa ndi mndandanda wazizindikiro zomwe zingawonetse kuchuluka kwa Hypoglycemia pang'ono: kugona, kugona, kuona, kusweka, chizungulire, thukuta, kugwedezeka, kuda nkhawa, kuda nkhawa, kugwedezeka m'manja, miyendo, milomo, kapena lilime, chizungulire, kulephera kukhazikika, kupweteka mutu , zisokonezo za kugona, kuda nkhawa, kuyankhula mothinana, kusakwiya, kuchita zamiseche, kusunthika kosasintha komanso kusintha umunthu. Ngati zizindikilo zoterezi zikuchitika, muyenera kudya nthawi yomweyo zakudya kapena zakumwa zomwe zimakhala ndi zosavuta monga maswiti kapena zakumwa zoziziritsa kukhosi. Izi zikuthandizira kuchuluka kwa shuga wamagazi, omwe amateteza thupi ku hypoglycemia yofatsa kapena yolimbitsa thupi. Nthawi zonse pamakhala chiopsezo cha hypoglycemia, matenda oopsa kwambiri omwe amafunikira foni mwachangu. Zizindikiro zake zimaphatikizapo kusokonezeka, kukomoka, kusazindikira komanso kufa. Chonde dziwani kuti nthawi zina, zizindikiro za hypoglycemia ndi zolakwika chifukwa cha uchidakwa.
Ndikofunikanso kuti muchepetse kugona chifukwa cha jakisoni wa insulin. Ichi ndi chizindikiro choyambirira cha hypoglycemia, ndi chizindikiro chomveka chakuti wosuta ayenera kudya zakudya zochulukirapo.
Nthawi zoterezi, sizikulimbikitsidwa kugona, chifukwa insulin imatha kusweka nthawi yopuma, ndipo kuchuluka kwa shuga m'magazi kumatha kutsika kwambiri. Popanda kudziwa izi, osewera ena ali pachiwopsezo chotenga matenda a hypoglycemia. Kuopsa kwa izi kwatchulidwa kale. Tsoka ilo, chakudya chamafuta ambiri asanagone sichikupindulitsa.Ogwiritsa ntchito omwe amayesa mankhwala a insulin ayenera kukhala atcheru nthawi yayitali ya mankhwalawo, komanso kupewa kugwiritsa ntchito insulin m'mawa kwambiri kuti pasachitike mankhwala osokoneza bongo usiku. Ndikofunika kuuza okondedwa anu za mankhwalawo kuti agwiritse ntchito ambulansi kuti athe kuzindikira. Izi zitha kuthandiza kupulumutsa nthawi yofunikira (mwina yofunika) pothandiza othandizira azaumoyo kuti azindikire ndi kulandira chithandizo.

Zotsatira za insulin

Mwa owerengeka ochepa, kugwiritsa ntchito insulin kumatha kupangitsa kuti ziwonekere kutulutsa komweko, kuphatikizapo kukwiya, kutupa, kuyabwa ndi / kapena kufiyanso pamalowo. Ndi chithandizo chakanthawi yayitali, zovuta za thupi zimatha kuchepa. Nthawi zina, izi zitha kukhala chifukwa cha zosakanikirana ndi mankhwala enaake, kapena, chifukwa cha insulin yoyambira nyama, kupukusa mapuloteni. Chochitika chocheperako koma chovuta kwambiri ndichomwe chimapangitsa kuti thupi lipatsidwe ndi insulin, zomwe zimaphatikizapo kuyenderera mthupi lonse, kupuma movutikira, kufupika mtima, kuchuluka kwa mtima, kuchuluka thukuta, komanso / kapena kuchepa kwa magazi. Nthawi zina, izi zimatha kukhala zowopsa pamoyo. Pakachitika zovuta zina, wogwiritsa ntchitoyo ayenera kuuzidwa kupita kuchipatala.

Makulidwe a insulin

Popeza pali mitundu ingapo ya insulini yogwiritsira ntchito mankhwalawa ndi mitundu yosiyanasiyana ya mankhwala, komanso zofunika kuchita ndi mankhwala osiyanasiyana, ndikofunikira kuti wogwiritsa ntchito adziwe kuchuluka kwake ndi nthawi ya insulini munjira iliyonse kuti athe kuthana ndi kuchuluka kwa ntchito, nthawi yayitali yochita, mlingo komanso kuchuluka kwa chakudya . Mu masewera, kukonzekera kwambiri kwa insulin komwe kumachitika (Novolog, Humalog and Humulin-R). Ndikofunika kutsindika kuti musanagwiritse ntchito insulin, ndikofunikira kuti mudziwe zochita za glucometer. Ichi ndi chida chachipatala chomwe chitha kudziwa mwachangu komanso molondola kuchuluka kwa shuga m'magazi. Chipangizochi chikuthandizira kuwongolera ndikukula kwa kudya kwa insulin / chakudya.

Mwachidule kuchita insulin

Mitundu ya insulin yocheperako (Novolog, Humalog, Humulin-R) cholinga chake ndi kubaya jakisoni wong'ambika. Pambuyo pakubaya kwapakati, jakisoniyo uyenera kusiyidwa wokhawokha, ndipo sayenera kutupidwa, kuti mankhwalawo asatulutsidwe mwachangu m'magazi. Ndikofunikanso kusintha tsamba la jekeseni wa subcutaneous kuti tipewe kudzikundikira mafuta ochulukitsa chifukwa champhamvu ya mahomoni. Mlingo wazachipatala udzasiyana malinga ndi zomwe wodwalayo ali nazo. Kuphatikiza apo, kusintha kwa zakudya, kuchuluka kwa zochitika, kapena ntchito / kugona mokwanira kumatha kukhudza mlingo wofunikira wa insulin. Ngakhale osavomerezeka ndi madotolo, ndikofunikira kupaka Mlingo wochepa wochita insulin intramuscularly. Komabe, izi zitha kupangitsa kuti chiwopsezo chiwonjezeke chifukwa cha kuperewera kwa mankhwalawo komanso zotsatira zake za hypoglycemic.
Mlingo wa insulin wa Athlete ungasiyane pang'ono, ndipo nthawi zambiri zimatengera zinthu monga kulemera kwa thupi, kuchepa kwa insulin, kuchuluka kwa zochitika, zakudya, komanso kugwiritsa ntchito mankhwala ena.
Ogwiritsa ntchito ambiri amakonda kumwa insulin mukangophunzitsidwa, nthawi yabwino kwambiri yogwiritsira ntchito mankhwalawo. Mwa omanga thupi, Mlingo wambiri wa insulin (Humulin-R) amagwiritsidwa ntchito kuchuluka kwa 1 IU pa 15-20 mapaundi amthupi, ndipo mlingo wofala kwambiri ndi mlingo wa 10 IU. Mlingowu umatha kuchepetsedwa pang'ono mwa ogwiritsa ntchito omwe ali ndi mankhwalawa Humalog ndi Novolog, omwe amapereka mphamvu mwamphamvu komanso mwachangu kwambiri. Ogwiritsa ntchito mankhwala a Novice nthawi zambiri amayamba kugwiritsa ntchito mankhwalawa pamiyeso yotsika ndikuwonjezeka kwapang'onopang'ono pamtundu woyenera. Mwachitsanzo, tsiku loyamba la mankhwala a insulin, wogwiritsa ntchito amatha kuyamba ndi 2 IU. Pambuyo pa gawo lililonse la maphunziro, mlingo umatha kuwonjezeredwa ndi 1ME, ndipo kuwonjezeka kumeneku kungapitilizebe mpaka muyeso womwe wokhazikitsa. Anthu ambiri amakhulupirira kuti kugwiritsa ntchito mankhwalawa ndi kotetezeka ndipo kumathandizanso kuganizira za momwe thupi limagwirira, popeza ogwiritsa ntchito amakhala ndi kulolera kosiyanasiyana kwa insulin.
Othamanga omwe amagwiritsa ntchito mahomoni akuchulukirachulukiridwe nthawi zambiri amagwiritsa ntchito mankhwala a insulin okwera pang'ono, popeza kukula kwa mahomoni kumachepetsa katulutsidwe ka insulin ndipo kumayambitsa kukana kwa ma insulin.
Kumbukirani kuti maola ochepa atatha kugwiritsa ntchito insulin ndikofunikira kudya zakudya zopatsa mphamvu. Ndikofunikira kudya osachepera magalamu khumi ndi anayi osavuta a chakudya 1 pa IU ya insulini (osagwiritsidwa ntchito mwachindunji magalamu 100, ngakhale mutamwa). Izi zikuyenera kuchitika pakadutsa mphindi 10-30 pambuyo povomerezeka ndi Humulin-R, kapena mukangogwiritsa ntchito Novolog kapena Humalog. Zakumwa zoziziritsa kukhosi nthawi zambiri zimagwiritsidwa ntchito ngati gwero lama chakudya ambiri. Pazifukwa zotetezeka, ogwiritsa ntchito ayenera kukhala ndi chidutswa cha shuga m'manja ngati magazi atagwera. Ochita masewera ambiri amakonda kupangaineineohohidrate ndi chakumwa chowonjezera chamafuta, chifukwa insulini ingathandize kukulitsa kupanga kwa minofu. 30-60 Mphindi atatha jakisoni wa insulin, wogwiritsa ntchito amafunika kudya bwino ndikudya phukusi la protein. Zakumwa zoziziritsa kukhosi ndi kugwedeza kwamapuloteni ndizofunikira kwambiri, chifukwa popanda izi, kuchuluka kwa shuga m'magazi kumatha kutsika kwambiri ndipo othamanga amatha kulowa mu chikhalidwe cha hypoglycemia. Zakudya zokwanira zama protein ndi mapuloteni ndimkhalidwe wokhazikika mukamagwiritsa ntchito insulin.

Kugwiritsa ntchito insulin pakati, nthawi yayitali, biphasic insulin

Zapakatikati zapakatikati, zazitali komanso za biphasic ndizobayira. Jakisoni wam'manja amathandizira kumasula mankhwalawa mwachangu, zomwe zingayambitse chiopsezo cha hypoglycemia. Pambuyo pakubaya jekeseni, malo operekera jekeseni ayenera kusiyidwa yekha, sayenera kuzitikita kuti mankhwalawo asatulutsidwe mwachangu kulowa m'magazi. Tikulimbikitsidwanso kusintha malo obaya jakisoni wambiri kuti tipewe kudzikundikira mafuta ochulukitsa chifukwa champhamvu ya mahomoni. Mlingo umasiyana malinga ndi zomwe wodwala aliyense ali nazo.
Kuphatikiza apo, kusintha kwa zakudya, kuchuluka kwa zochitika, kapena ntchito / kugona mokwanira kungakhudze mlingo wa insulin. Ma insulini apakatikati, ochita masewera othana ndi biphasic sogwiritsidwa ntchito kwambiri pamasewera chifukwa cha chikhalidwe chawo chokhala ndi nthawi yayitali, zomwe zimawapangitsa kuti asamagwiritsidwe ntchito moyenera pambuyo pa maphunziro, omwe amadziwika ndi kuchuluka kwa michere.

Kupezeka:

Ma insulin a U-100 akupezeka kuchokera ku malo ogulitsa ogulitsa-ku United States. Chifukwa chake, odwala matenda ashuga omwe amadalira insulin ali ndi mwayi wosavuta wopeza mankhwalawa opulumutsa moyo. Insulin Yogundika (U-500) imagulitsidwa ndi mankhwala okha. M'madera ambiri padziko lapansi, kugwiritsa ntchito mankhwalawa kwakadali kovuta kumabweretsa mosavuta komanso mitengo yotsika pamsika wakuda. Ku Russia, mankhwalawa amapezeka pamankhwala.