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▎ Imiterere ya GLP-3
Inkomoko: PubChem |
Urukurikirane: YA⊃1; QGTFTSDYSI-L⊃2; LDKK⁴AQA⊃1; AFIEYLLEGGPSSGAPPPS⊃3; Inzira ya molekulari: C 221H 342N 46O.68 Uburemere bwa molekuline: 4731 g / mol Numero ya CAS: 2381089-83-2 PubChem CID: 171390338 Synonyme ： LY3437943 |
L GLP-3 Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na GLP-3?
Umubyibuho ukabije ni kimwe mu bibazo bikomeye by’ubuzima rusange muri iki gihe. Umubyibuho ukabije urashobora gutera ibibazo bitandukanye byubuzima, nka metabolism yo mu bwoko bwa 2, indwara zifata umutima, hypertension, dyslipidemia, nindwara zumwijima zidafite inzoga. Hamwe n’ubwiyongere bukabije bw’umubyibuho ukabije, hagenda hakenerwa ubuvuzi bushya bushobora gucunga neza ibiro by’umubiri no kuzamura ubuzima [1] . Nubwo guhindura imibereho, nko kongera imyitozo ngororamubiri no kugabanya ibiryo, nuburyo bwibanze bwo gucunga ibiro, kubungabunga igihe kirekire kugabanya ibiro bikomeje kuba ingorabahizi kubantu benshi bakuze. GLP-3 ni igitabo gishya cyitwa reseptor agonist ikora kuri reseptor ya glucagon imeze nka peptide-1 (GLP-1R), reseptor ya glucose iterwa na insulineotropique polypeptide (GIPR), na reseptor ya glucagon (GCGR). Ubu buryo bwinshi-bwakirwa bwibikorwa butanga inyungu zidasanzwe mugutakaza ibiro. Ugereranije n’imiti igabanya ibiro ikora kuri reseptor imwe, GLP-3 irashobora kurushaho kugenzura imikorere yimikorere yumubiri [1] . GLP-3 igera ku kugabanya ibiro igenga imisemburo myinshi. Ntabwo igira ingaruka zikomeye zo kugabanya ibiro gusa ahubwo ifite n'ingaruka zoroheje zo munda. Byongeye kandi, ugereranije nindi miti mishya yo kugabanya ibiro, GLP-3, nka tronc reseptor agonist, ifite ingaruka zikomeye zo kugabanya ibiro hamwe nabantu benshi bakoreshwa.
Ni ubuhe buryo bwo gukora bwa GLP-3?
Uburyo bwibikorwa bya GLP-3 buturuka ahanini ku ngaruka zabwo za agonistic kuri reseptors nyinshi. Ubwa mbere, ingaruka za agonistic kuri reseptor ya glucagon isa na peptide-1 (GLP-1R) yongera imisemburo ya insuline, ikabuza gusohora glucagon, igabanya urugero rwa glucose mu maraso, kandi icyarimwe igatinda gusohora gastrica, ikongera guhaga, kandi igabanya gufata ibiryo [2] . Icya kabiri, ingaruka za agonistic kuri glucose iterwa na glucose ya insuline ya polypeptide (GIPR) irashobora guteza imbere gusohora insuline, kongera ikoreshwa rya glucose, kandi ikagira ingaruka kuri metabolisme yibinure, ikabuza lipolysis no guteza imbere ibinure [2] . Byongeye kandi, nubwo ingaruka za agonistic ya GLP-3 kuri reseptor ya glucagon (GCGR) ubusanzwe itera glycogenolysis na gluconeogenezi mu mwijima, ikongera urugero rwa glucose yamaraso, bitewe na GLP-3, iyi ngaruka yo kongera glucose yamaraso ikurwaho ningaruka zabandi bakira. Muri icyo gihe, itera lipolysis kandi igabanya kwirundanya kw'amavuta [2] . Ubu buryo bwibikorwa byinshi birashobora kuba byiza mukuvura umubyibuho ukabije kuruta reseptor agonist.
Mugukoresha icyarimwe gukora ibyo byakira bitatu, GLP-3 irashobora kugira ingaruka zitandukanye zoguhindura metabolike kandi ikanatanga ingaruka zo kuvura umubyibuho ukabije nindwara zifitanye isano. Mu rwego rwo kugenzura urugero rwa glucose yamaraso, bitewe nogukora kwa GLP-1R na GIPR biteza imbere gusohora insuline no kubuza gusohora glucagon, no gukora GCGR bikarangizwa ningaruka zabandi bakira, GLP-3 irashobora kugenzura neza urugero rwa glucose yamaraso, bifite akamaro kanini mukuvura metabolism yo mu bwoko bwa 2 [1, 2] . Mu rwego rwo kugabanya kwegeranya ibinure, gukora kwa GCGR bitera lipolysis no kugabanya ibinure. Muri icyo gihe, gukora kwa GLP-1R byongera guhaga no kugabanya gufata ibiryo, bikagabanya no guhuza ibinure [1, 2] . Byongeye kandi, GLP-3 nayo igira ingaruka nziza ku ndwara zumwijima zidafite inzoga. Irashobora kugabanya ibinure byumwijima no kunoza imikorere yumwijima. Ikigeragezo cyateguwe, gihumye-impumyi, igenzurwa na platbo cyerekanye ko impuzandengo ugereranije n’amavuta y’umwijima mu itsinda ry’ubuvuzi rya GLP-3 mu byumweru 24 yari hasi cyane ugereranije n’ay'itsinda rya placebo [3].
HbA1c, uburemere bwumubiri, umuvuduko wamaraso, na lipide Data ni byibuze-kare bisobanura (hamwe nibibari byerekana SE) uhereye kubisesengura ryakozwe, keretse bivuzwe ukundi.
Inkomoko: PubMed [4]
Nigute mubyukuri GLP-3 igenga glucose metabolism nyuma yo gukora reseptors eshatu?
GLP-3 igenga glucose yamaraso ikoresheje uburyo bwinshi, harimo gukora GLP-1 na GIP yakira, gutera insuline gusohora, kubuza gusohora glucagon, gutinda gusohora gastrica, kugenzura metabolisme y’ibinure, no kugabanya urwego rwa ANGPTL3 / 8. Ku bijyanye no kugenzura amaraso ya glucose, GLP-3 ikora kuri reseptor ya GLP-1 na GIP, igateza imbere sensibilité ya selile pancreatic β selile ya glucose, guhuza no kurekura insuline, hanyuma igateza imbere gufata no gukoresha glucose mu mitsi, kugera ku ngaruka zo kugabanya glucose yamaraso [4, 5] .Mu bushakashatsi bwakozwe ku barwayi ba metabolisme yo mu bwoko bwa 2, GLP-3 yerekanye ingaruka zikomeye zo kugabanya insimburangingo ya Hlog. gusohora (Rosenstock J, 2023). Muri icyo gihe, gukora reseptor ya GLP-1 birashobora kubuza gusohora glucagon na selile pancreatic α selile, bikarinda glucose yamaraso kuba hejuru cyane. Mu bushakashatsi bw’ubuvuzi, byagaragaye ko urugero rwa glucagon rw’abarwayi bakoresha GLP-3 rwaragabanutse, ari nabwo rufasha gukomeza umutekano w’amaraso glucose [4, 5] . Gukora reseptor ya GLP-1 na GIP birashobora kandi gutinza umuvuduko wo gusiba gastrica, kugabanya igogorwa ryokunywa no gufata ibiryo, kandi bikagabanya izamuka rikabije ryamaraso ya glucose nyuma yinyuma. Ubushakashatsi bwerekanye ko igihe cyo gufungura igifu cy’abarwayi bavuwe na GLP-3 cyongerwa cyane nyuma yo kurya, bityo bikagabanya agaciro k’imisemburo ya glucose nyuma yo kubyara [4].
Kugena ibinure bya metabolisme na GLP-3 nabyo bigira ingaruka ku buryo butaziguye glucose metabolism. Kurugero, mubushakashatsi bwakozwe nabarwayi bafite umubyibuho ukabije, byagaragaye ko GLP-3 ishobora kugabanya urugero rwa triglyceride (TG), lipoprotein nkeya (LDL), hamwe na cholesterol ya lipoproteine (VLDL) nkeya cyane [2, 6] . Iri terambere rya metabolisme ya lipide rishobora kuba rifitanye isano no kunoza insuline, bityo bikagira uruhare mu kurwanya amaraso glucose. By'umwihariko, nyuma yo kuvurwa kwa GLP-3, plasma 3-hydroxybutyric aside (3-HB) iriyongera, iherekejwe no kwiyongera kwa 3-hydroxybutyrylcarnitine (C 4OH), igipimo cya acetylcarnitine na karnitine yubusa (C 2/ C 0), hamwe na acylcarnitine y’umunyururu uciriritse, byerekana ko lipolysis yiyongereye kuri aside ya adipose.
GLP-3 irashobora kandi kugabanya dihydroceramide yose (DhCers), kandi iri hinduka rifitanye isano no kunoza insuline, kugabanya indwara ya hepatike, hamwe no gutwika sisitemu [6] .Mu gihe kimwe, GLP-3 irashobora kandi kugabanya ubukana bw’ikigo cya ANGPTL3 / 8 muri serumu y’abarwayi ba metabolism yo mu bwoko bwa 2, ikagenga metabolism ya glucose . ANGPTL3 / 8 nuburyo bwiza bwo gukwirakwiza lipoprotein lipase (LPL), kandi urwego rwa serumu rufitanye isano itaziguye na TG hamwe na cholesterol ya lipoprotein nkeya (LDL-C). GLP-3 igabanya urwego rwa ANGPTL3 / 8, ishobora kugenga metabolisme glucose igabanya lipoproteine ikungahaye kuri triglyceride [7] .
Ni mu buhe buryo GLP-3 yerekana ingaruka zayo?
Ingaruka zikomeye zo kugabanya ibiro:
GLP-3 yerekanye ingaruka zikomeye zo kugabanya ibiro mubigeragezo byinshi byamavuriro. Kurugero, mubushakashatsi bwamavuriro burimo abantu bakuru 338 [2] , abarwayi bavuwe bafite dosiye zitandukanye za GLP-3 bagize ibiro byinshi mubyumweru 48. Muri bo, abarwayi bo mu itsinda rya 12mg dose bafite ibiro 24.2%, kandi umubare munini w'abarwayi bageze ku biro bitandukanye. Kurugero, mubarwayi bahabwa dosiye ya 4mg, 8mg, na 12mg, 92%, 100%, na 100% byabarwayi batakaje 5% cyangwa barenga ibiro byumubiri. Mu bundi bushakashatsi [8] , ibigeragezo bibiri byateganijwe byateganijwe birimo abarwayi ba metabolisme yo mu bwoko bwa 353 bwerekanye ko ugereranije na placebo, GLP-3 ishobora kugabanya cyane ibiro by’umubiri by’abarwayi ku gipimo cya 11.89 kandi ikagabanya na gemoglobine (HbA1C). Byongeye kandi, mu igeragezwa ry’abarwayi bakuze bafite umubyibuho ukabije utarwaye diyabete, GLP-3 yateje ibiro 24.2% ku barwayi, naho 83% by’abarwayi batakaje 15% cyangwa birenga ibiro by’umubiri mu byumweru 48. Ibisubizo byerekana ko GLP-3 ifite amahirwe menshi yo kugabanya ibiro.
Kuvura ubwoko bwa 2 metabolism :
GLP-3 irerekana kandi ubushobozi bumwe na bumwe bwo kuvura metabolism yo mu bwoko bwa 2. Mu bigeragezo bimwe na bimwe by’amavuriro, GLP-3 yerekanye igabanuka rya glycated hemoglobine (HbA1c) no kugabanuka bitewe n’ibiro. Kurugero, mubushakashatsi bumwe, mubarwayi ba metabolisme yo mu bwoko bwa 2, GLP-3 yerekanye ingaruka zikomeye zo kugenzura glucose yamaraso, kugabanya gemoglobine glycated 1,64% ugereranije na placebo [4, 8] . Byongeye kandi, mu igeragezwa ryateganijwe, rihumye-impumyi, umwanya wawo, hamwe n’igenzura-rigereranywa n’itsinda ryiciro rya 2, icyitegererezo cy’inyamanswa zifite metabolisme yo mu bwoko bwa 2 cyerekanye ko igabanuka ryinshi rya gemoglobine ya glycated ndetse no kugabanuka bitewe n’ibiro nyuma yo guhabwa GLP-3 [4] . Ibi birashobora guterwa ningaruka zuzuye zibiyobyabwenge kuri GLP-1, GCGR, na GIPR, bitezimbere glucose metabolism hamwe nuburinganire bwingufu.
Gutezimbere ibintu bishobora gutera umutima-mitsi:
GLP-3 ntishobora kugabanya ibiro byumubiri gusa ahubwo inatezimbere ibintu bishobora gutera ibyago byumutima nimiyoboro yumutima, nka serumu lipid profil hamwe na glycated hemoglobine. Ibi byerekana isano iri hagati yumubyibuho ukabije nindwara zifata umutima, kandi GLP-3 irashobora guteza imbere ubuzima bwumutima nimiyoboro yabarwayi bafite umubyibuho ukabije binyuze munzira nyinshi. Kurugero, kugabanya urwego rutari HDL-C, apoB, na LDLP birashobora kugabanya ibyago byo kurwara aterosklerose; kugabanya urugero rwa glycated hemoglobine birashobora kunoza igenzura rya glucose yamaraso kubarwayi ba metabolism, bityo bikagabanya ibyago byo kurwara umutima nimiyoboro y'amaraso [8-10] .
Kuvura indwara zumwijima zidafite inzoga (NAFLD):
GLP-3 ni igitabo gishya cya reseptor agonist peptide yibasira reseptor ya glucagon (GCGR), reseptor ya glucose iterwa na insuline ya polotipide (GIPR), hamwe na glucagon imeze nka peptide-1 (GLP-1R). Ubushakashatsi bwerekanye ko GLP-3 ifite ubushobozi bwo kuvura indwara zumwijima zidafite inzoga. Mu bushakashatsi bumwe, ubushakashatsi bwakozwe ku bushake, buhumye-buhumyi, bugenzurwa na platbo bumara ibyumweru 48 bwakorewe ku bitabiriye amahugurwa bafite imikorere mibi ya metabolike idakira ifitanye isano n’indwara y’umwijima n’amavuta y’umwijima ≥10%. Ibisubizo byagaragaje ko mu byumweru 24, impuzandengo y’amavuta y’umwijima ugereranije n’ibanze mu bitabiriye amahugurwa bavuwe na dosiye zitandukanye za GLP-3 (1mg, 4mg, 8mg, na 12mg) bari -42,9%, -57.0%, -81.4%, na -82.4%, mu gihe mu itsinda rya placebo ryari + 0.3% [3] . Ibi byerekana ko GLP-3 ishobora kugira ingaruka zikomeye zo kuvura indwara zumwijima zidafite inzoga.
Mu gusoza, nk'igitabo gishya cya reseptor agonist, GLP-3 yerekana imbaraga zikomeye zo kuvura umubyibuho ukabije n'indwara zifitanye isano. Irashobora gukora reseptor ya glucagon, reseptor ya glucose iterwa na insulinotropique polypeptide, hamwe na reseptor ya glucagon imeze nka peptide-1, igenga byimazeyo metabolism yumubiri kuva mubice byinshi, kunoza glucose yamaraso, kugabanya ibiro byumubiri, no kugenzura metabolisme ya lipide. Kugaragara kwa GLP-3 bizana uburyo bushya bwo kuvura abarwayi bafite umubyibuho ukabije, ubwoko bwa 2 metabolism, nizindi ndwara. Biteganijwe ko izaca ku mbibi z’imiti gakondo ya reseptor agonist, itanga intwaro ikomeye yo gukemura ibibazo bikabije by’umubyibuho ukabije n’indwara ziterwa na metabolike, guteza imbere iterambere ry’ubuvuzi bijyanye, kuzamura imibereho y’abarwayi, no kugabanya umutwaro w’ubuvuzi.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Rosenstock J ni intiti ikomeye cyane mubuvuzi, ikorana cyane ninzego nka kaminuza yubuvuzi ya kaminuza ya Texas Southwestern na kaminuza ya Texas Dallas. Akora kandi ubushakashatsi mubigo nka Centre ya VIGOR yo muri Kanada na Veloc Clin Res Ctr Med City. Ubushakashatsi bwe bwibanze kuri endocrinology na metabolism, sisitemu yumutima nimiyoboro yumutima na kardiologiya, farumasi, nubuvuzi bwikigereranyo, yibanda kuri metabolism, umubyibuho ukabije, hamwe nubuvuzi bujyanye no guteza imbere ibiyobyabwenge. J Rosenstock yageze ku ntera ishimishije mu buvuzi bw’amavuriro, yiswe Umushakashatsi uvugwa cyane kuva mu 2017 kugeza mu 2024.Ibyo byerekana ingaruka zikomeye no kumenyekanisha ibikorwa bye. Abinyujije ku bufatanye n’ibigo byinshi by’ubushakashatsi, yahinduye neza ibyavuye mu bushakashatsi mu bikorwa by’ubuvuzi, agirira akamaro abarwayi bafite indwara ziterwa na metaboliya n’umutima ndetse no guteza imbere ubumenyi bw’ubuvuzi. Rosenstock J yanditse kurutonde rwerekana [4].
