Na Cocer Peptides 
hashize iminsi 13
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Umubyibuho ukabije ugenda urushaho kuba ikibazo gikomeye ku isi, ntigire ingaruka ku buzima bw’umubiri gusa ahubwo inagira uruhare runini mu ndwara zidakira nk’indwara zifata umutima ndetse na diyabete yo mu bwoko bwa 2. Kubona uburyo bwiza bwo kugabanya ibiro byabaye intego yibanze mubushakashatsi bwubuvuzi. Tizepatide ni imiti ikora ku byakira byombi, itanga uburyo bushya bwo kuvura umubyibuho ukabije.
Igishushanyo 1: Imiterere nintambwe yambere ya molekulari yerekana binyuze muri GIPR na GLP1R muri GIPR - GLP1R ebyiri agoniste RG7697 - NNCOO90-2746 na LY3298176.
Tizepatide ya kabiri yakira Agonist Mechanism
(1) GIP Receptor Agonist Mechanism
Ishingiro rya Physiologique ya GIP yakira
GIP reseptor ni reseptor selile yihariye iboneka mubice byinshi, harimo pancreas, tissue adipose, umwijima, n'imitsi. Ku buso bwa pancreatic islet β selile, iyo imisemburo ya GIP ihujwe niyi reseptor, ikora inzira yerekana ibimenyetso byerekana ibimenyetso, biganisha ku kwiyongera kurwego rwa cAMP. cAMP noneho ikora protein kinase A, ikoresheje urukurikirane rwibisubizo, itera gusohora insuline.
Muri tipusi ya adipose, gukora kwa reseptor ya GIP bigenga metabolism ya adipocyte. Itera glucose gufata na adipocytes, ikongerera aside aside hamwe nububiko, ikanabuza lipolysis. Ubushakashatsi bwerekana ko iyi nzira ishobora kuba ifitanye isano no kwiyongera kwabatwara glucose (GLUT4), byorohereza glucose kwinjira muri adipocytes, bitanga ibikoresho fatizo byo gusanisha amavuta.
Ingaruka za Tizepatide kuri GIP yakira
Tizepatide ifite imiterere isa na hormone ya GIP kandi irashobora guhuza cyane no gukora reseptor ya GIP. Ugereranije na endogenous GIP, Tizepatide ifite isano ikomeye ihuza abayakira, igafasha gukora neza inzira zerekana inzira. Ubushakashatsi bwerekanye ko nyuma yo guhuza ababyakira, bishobora kongera urugero rwa cAMP, bityo bikarushaho gutera imbere gusohora insuline. Muri tipusi ya adipose, kugenzura neza metabolism ya lipide nyuma yo gukora reseptor ituma glucose ifata na adipocytes hamwe na synthesis iringaniye hamwe no kubika aside irike, ikarinda amavuta menshi - ikintu gikomeye mugukomeza metabolisme isanzwe.
Igishushanyo 2: Ingaruka zigereranya za RG7697 / NNCOO90-2746 na LY3298176 zivuye mubigeragezo byamavuriro, usibye aho inyenyeri zerekana (zerekanwa gusa nimbeba).
(2) Uburyo bwo Gukora GLP-1
Ishingiro ryimiterere ya GLP-1
GLP-1 reseptor nayo ni reseptor ya selile ikwirakwizwa cyane cyane muri pancreatic β selile, gastrointestinal tract, n'ubwonko. Muri pancreatic β selile, GLP-1 ihuza reseptor kandi igakora inzira yerekana ibimenyetso kugirango insuline isohore. Bitandukanye na GIP, ingaruka za GLP-1 zigengwa nurwego rwa glucose yamaraso: itera gusohora insuline mugihe glucose yamaraso ari nyinshi kandi ingaruka zayo zigabanuka mugihe glucose yamaraso ari ibisanzwe, bigatuma itekana.
Mu nzira ya gastrointestinal, gukora reseptor ya GLP-1 byongerera kugaburira ibiryo mu gifu, bikarinda umuvuduko ukabije wamaraso glucose, kandi bikanabuza gusohora aside gastric, kurinda mucosa gastrointestinal. Mu bwonko, ikora ku turere tugenzura ubushake bwo kurya, kugabanya inzara no kongera guhaga, bityo bigatuma ibiryo bigabanuka.
Ingaruka za Tizepatide kuri reseptor ya GLP-1
Tizepatide ifite isano ikomeye yo kwakira GLP-1, kandi iyo ikora, itanga ingaruka zisa nizo za endogenous GLP-1. Kubijyanye no kugenzura amaraso glucose, itera gusohora insuline ishingiye ku gipimo cya glucose yamaraso, bityo ikagenzura neza glucose yamaraso. Mu nzira ya gastrointestinal, ingaruka zayo zo gutinda gusiba gastrica zigaragara cyane kuruta iz'imiti gakondo. Mu bwonko, ingaruka zayo zo kugabanya ubushake bwo kurya ziraramba cyane, zifasha kugabanya ibiro.
(3) Ingaruka zoguhuza zibiri zakira Agonism
Ingaruka zoguhuza mumaraso Glucose
Tizepatide ikora kuri reseptor ya GIP na GLP-1, bigatuma glucose igenga neza. GIP itera cyane cyane gusohora insuline mugihe cyambere cyo kubyara, kugabanya glucose yamaraso; GLP-1 ikomeje gukora mugihe cyinyuma yinyuma, ntabwo itera gusohora insuline gusa ahubwo inadindiza gusiba gastrica, kugabanya gufata ibiryo, no gukomeza glucose yamaraso. Gukora reseptors byombi icyarimwe bivamo uburyo bwiza bwo kugenzura amaraso glucose nyuma yo gutangira. Kurugero, mubushakashatsi bwinyamaswa za diyabete, Tizepatide yagabanije glucose yamaraso nyuma yinyuma yiyongera kuruta imiti ya GIP cyangwa GLP-1 yonyine, kandi glucose yamaraso yagarutse mubisanzwe byihuse.
Ingaruka zoguhuza imbaraga zingirakamaro
Ku bijyanye ningufu za metabolisme, GIP reseptor agonist iteza glucose gufata selile, ariko iyo Tizepatide iyobowe na synthesis, ibinure ntibirundanya cyane. Hagati aho, GLP-1 reseptor agonist igabanya ubushake bwo kurya, kongera guhaga, kugabanya gufata kalori, no guteza imbere gutwika amavuta no gukoresha ingufu. Iki gikorwa cyibiri kiringaniza gufata no gukoresha. Kurugero, mubushakashatsi bwinyamaswa zifite umubyibuho ukabije, nyuma yo gukoresha Tizepatide mugihe runaka, uburemere bwumubiri winyamaswa bwaragabanutse, ibinure byumubiri bigabanuka, kandi metabolism yibanze yihuta.
Igishushanyo 3: Itandukaniro hagati ya agergiste ya synergiste (chimeras) nuburyo bwa peptide fusion
Gukoresha Tizepatide mukuvura umubyibuho ukabije
(1) Ingaruka zo Gutakaza Ibiro
Ibimenyetso byubushakashatsi bwibanze
Mu bushakashatsi bw’inyamaswa, imbeba zifite umubyibuho ukabije zatanzwe na Tizepatide zerekanaga kugabanuka gahoro gahoro mugihe, hamwe no kugabanuka kugaragara ugereranije nitsinda rishinzwe kugenzura. Isesengura ry’amavuta yo mu mubiri ryagaragaje ko ritagabanije ibinure gusa ahubwo ko ryanagabanije gukwirakwiza ibinure, bigabanya ibinure byinjira mu mubiri. Uburyo bwibanze ni bubiri: icya mbere, gukora reseptor ya GLP-1 birwanya ubushake bwo guhagarika inzara yubwonko; icya kabiri, iteza ibinure kandi ikongera ingufu zikoreshwa.
Ibimenyetso byo kugerageza
Mu bigeragezo bivura byibasira abarwayi bafite umubyibuho ukabije, Tizepatide yanagaragaje ingaruka nziza zo kugabanya ibiro. Ibigeragezo byinshi byateganijwe byerekanaga ko nyuma yigihe cyo kuvurwa, ibiro by abarwayi byagabanutse cyane. Kurugero, mubigeragezo byibyumweru 24, itsinda ryokuvura ryagabanutseho ibiro hafi 10%, mugihe itsinda rya placebo ryerekanye impinduka nke. Byongeye kandi, kuzenguruka mu rukenyerero rw’abarwayi no kuzenguruka mu kibuno na byo byagabanutse, byerekana ko bidatera kugabanya ibiro gusa ahubwo binagabanya ikwirakwizwa ry’ibinure kandi bigabanya ibyago by’indwara ziterwa n'umubyibuho ukabije.
(2) Gutezimbere Indwara ya Syndrome ya Metabolike
Kunoza Amaraso Glucose
Abarwayi bafite umubyibuho ukabije bakunze kugira ibibazo bya glucose yamaraso, kandi Tizepatide itezimbere glucose yamaraso mugihe itera kugabanuka. Mu bigeragezo by’amavuriro, abarwayi bagabanutse cyane mu maraso glucose yisonzesha, glucose yamaraso nyuma yo kwandura, na hemoglobine A1c (ikimenyetso cyerekana igihe kirekire cyo kugenzura amaraso glucose) nyuma yo kuvurwa. Ni ukubera ko ikora binyuze muburyo bubiri bwo kwakirwa, guteza imbere gusohora kwa insuline no kongera insuline, ndetse ikanadindiza ubusa igifu no kugabanya ibiryo byihuse. Ugereranije n'imiti gakondo ya antidiabete, ntabwo igabanya glucose yamaraso gusa ahubwo inatera kugabanya ibiro, itanga inyungu nyinshi kubarwayi bafite umubyibuho ukabije barwaye diyabete.
Kunoza amabwiriza ya Lipid
Umubyibuho ukabije ukunze guherekezwa na dyslipidemiya, nka triglyceride yazamutse hamwe na lipoproteine (HDL) ikabije. Tizepatide irashobora kugenga lipide: nyuma yubuyobozi, abarwayi bahuye nigabanuka rya triglyceride kandi bongera HDL. Ibi birashobora kuba bifitanye isano nogutegekanya metabolisme ya lipide, nko guteza glucose ifata ingirabuzimafatizo, kugabanya aside irike, no kongera okiside yibinure, bityo bikanonosora imyirondoro ya lipide no kugabanya ibyago byindwara z'umutima.
(3) Inyungu zishoboka kuri sisitemu yumutima nimiyoboro
Kugenzura umuvuduko wamaraso
Umubyibuho ukabije ni kimwe mu bintu bishobora gutera hypertension. Ubushakashatsi ku mavuriro bwerekanye ko nyuma yo kuvurwa na Tizepatide, umuvuduko w’amaraso wa systolique na diastolique byombi bigabanuka. Ibi birashobora kuba bifitanye isano no kugabanya ibiro no kunoza metabolisme: kugabanya ibiro bigabanya umutwaro ku mutima, kandi kuzamura glucose yamaraso hamwe na lipide bifasha kugarura ubuzima bwimitsi no kugabanya kurwanya imitsi. Byongeye kandi, ingaruka zayo mu nzira ya gastrointestinal irashobora kugira uruhare rutaziguye ku mikorere ya neuroendocrine, bityo bikagenga umuvuduko wamaraso.
Ingaruka zo gukingira imitsi
Indwara idakira hamwe na stress ya okiside ikunze kugaragara ku barwayi bafite umubyibuho ukabije, ishobora kwangiza endotelium y'amaraso kandi igatera aterosklerose. Tizepatide irinda endotelium y'amaraso mu kunoza metabolisme, kugabanya irekurwa ry'ibintu bitera umuriro, no kugabanya imihangayiko ya okiside. Ubushakashatsi bwerekana ko nyuma yo kuvurwa, ibimenyetso by’abarwayi nka C-reaction proteine (CRP) byagabanutse, kandi ibimenyetso byerekana imikorere y’imitsi iva mu maraso nka aside nitide irekurwa byiyongera, bikaba byerekana ko ubuzima bw’imitsi bwateye imbere ndetse no gufasha mu gukumira indwara zifata umutima.
Umwanzuro
Tizepatide yerekana ubushobozi bukomeye mukuvura umubyibuho ukabije icyarimwe ikora kuri reseptor ya GIP na GLP-1. Ntabwo iteza imbere gusa kugabanya ibiro ahubwo inatezimbere ibipimo bya metabolike nka glucose yamaraso hamwe na lipide, mugihe itanga uburinzi bwumutima. Binyuze muburyo butandukanye bwibikorwa, itanga uburyo bushya bwo kuvura umubyibuho ukabije hamwe nibibazo bifitanye isano.
Inkomoko
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[2] Jensen TL, Nden ABO, Karstoft K, n'abandi. Tirzepatid. Dual GLP-1 / GIP reseptor agonist, Kuvura diyabete yo mu bwoko bwa 2 n'umubyibuho ukabije [J]. Ibiyobyabwenge by'ejo hazaza, 2023. DOI: 10.3389 / fendo.2022.1004044
[3] Willard FS, Douros JD, Gabe MB, n'abandi. Tirzepatid ni impirimbanyi kandi ibogamye ya GIP na GLP-1 reseptor agonist [J]. Ubushishozi bwa Jci, 2020,5 (17) .DOI: 10.1172 / jci.ubushishozi.140532.
] Indwara ya Diyabete Syndrome hamwe n'umubyibuho ukabije-Intego no kuvura, 2019,12: 1973-1985.DOI: 10.2147 / DMSO.S191438.
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