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G GLP-3 Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na GLP-3?
Umubyibuho ukabije wabaye imwe mu mbogamizi zikomeye z’ubuzima rusange muri sosiyete ya none. Irashobora kubyara ibibazo byinshi byubuzima nkubwoko bwa 2 metabolism mellitus, indwara zifata umutima nimiyoboro, hypertension, dyslipidemia, nindwara zumwijima zidafite inzoga. Hamwe n’ubwiyongere bukabije bw’umubyibuho ukabije, hakenewe byihutirwa ubuvuzi bushya bushobora gucunga neza ibiro by’umubiri no kuzamura ubuzima [1] . Nubwo ibikorwa byubuzima, nko kongera imyitozo ngororamubiri no kugenzura imirire, nizo ngamba zingenzi zo kugabanya ibiro, biragoye cyane kubarwayi benshi bafite umubyibuho ukabije gukomeza kugabanya ibiro birebire.
GLP-3, nkibintu bitatu byakira reseptor agonist, irashobora gukora kuri glucagon imeze nka peptide-1 yakira (
GLP-1R), glucose-iterwa na insulinotropic polypeptide reseptor (GIPR), hamwe na glucagon reseptor (GCGR). Ubu buryo bwinshi-bwakirwa bwibikorwa bubaha ibyiza byingenzi murwego rwo kugabanya ibiro. Ugereranije n’imiti igabanya ibiro ikora kuri reseptor imwe gusa, GLP-3 irashobora kurushaho kugenzura imikorere yimikorere yumubiri [1] . GLP-3 igera ku kugabanya ibiro mu kugenzura imisemburo myinshi ya hormone, ntigaragaza gusa imbaraga zidasanzwe ahubwo inagira ingaruka zoroheje zo mu gifu. Byongeye kandi, nka tronc reseptor agonist, GLP-3 ifite imbaraga zikomeye zo kugabanya ibiro hamwe nabantu benshi bakoreshwa ugereranije nindi miti mishya yo kugabanya ibiro.
GLP-3 ni iki?
GLP-3 ni igitabo gishya gikora glucagon-isa na peptide-1 (GLP-1) reseptor agonist. Yahinduwe kandi itezimbere hashingiwe ku miterere ya GLP-1 karemano, kandi irashobora guhuza cyane no gukora reseptor ya GLP-1, ikora imirimo ya physiologique isa niy'imiterere ya GLP-1, nko guteza imbere imisemburo ya insuline, kubuza gusohora glucagon, gutinda gusohora gastrica, kugabanya ubushake bwo kurya, n'ibindi. Ifite ibyifuzo byinshi byo kuvura metabolism no gucunga ibiro.
Ni ubuhe buryo bwo gukora bwa GLP-3?
Uburyo bwibikorwa bya GLP-3 buturuka ku ngaruka zabwo za agonistic kuri reseptors nyinshi. Ubwa mbere, ingaruka ziterwa na agonistic kuri reseptor ya glucagon isa na peptide-1 (GLP-1R) irashobora kongera imisemburo ya insuline, ikabuza gusohora glucagon, kugabanya glucose yamaraso, kandi icyarimwe igatinda gusohora gastrica, kongera guhaga, no kugabanya ibiryo [2] . Icya kabiri, ingaruka ziterwa na agonistic kuri glucose iterwa na insuline ya insuline ya polypeptide ya reseptor (GIPR) irashobora guteza imbere gusohora insuline, kongera ikoreshwa rya glucose, no kugira ingaruka ku mavuta ya metabolisme, ikabuza lipolysis no guteza imbere ibinure [2] . Byongeye kandi, ingaruka za agonistic ya GLP-3 kuri reseptor ya glucagon (GCGR) ubusanzwe itera glycogenolysis na gluconeogenezi mu mwijima, bikongera urugero rw'amaraso glucose. Ariko, mugikorwa cya GLP-3, iyi ngaruka yo kuzamura glucose ikurwaho ningaruka zabandi bombi bakira, mugihe iteza lipolysis no kugabanya ibinure [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, kubera ko gukora kwa GLP-1R na GIPR bitera gusohora insuline kandi bikabuza gusohora glucagon, kandi gukora GCGR bikurwaho n’ingaruka z’abandi bakira, GLP-3 irashobora kugabanya neza urugero rwa glucose y’amaraso, ifite akamaro kanini mu kuvura indwara ya metabolism yo mu bwoko bwa 2 [1, 2] . Mu rwego rwo kugabanya kwegeranya ibinure, gukora kwa GCGR bitera lipolysis kandi bikagabanya kwegeranya ibinure, mugihe gukora GLP-1R byongera guhaga no kugabanya ibiryo, bikagabanya no gusanisha amavuta [1] . Byongeye kandi, GLP-3 nayo igira ingaruka nziza ku ndwara zumwijima zidafite inzoga. Irashobora kugabanya ibinure byumwijima no kunoza imikorere yumwijima.
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]
Ni mu buhe buryo GLP-3 yerekana ingaruka zayo?
GLP-3 yerekana ingaruka zikomeye mubice byinshi
Ingaruka zikomeye zo kugabanya ibiro: GLP-3 yerekanye ingaruka zikomeye zo kugabanya ibiro mubigeragezo byinshi byamavuriro. Kurugero, mubushakashatsi bwamavuriro burimo abantu bakuru 338 (Jastreboff AMM, 2023), abarwayi bavuwe bafite dosiye zitandukanye za GLP-3 bagize ibiro byinshi mubyumweru 48. Muri bo, abarwayi bo mu itsinda rya 12mg dose batakaje 24.2% by'uburemere bw'umubiri wabo, kandi umubare munini w'abarwayi bagabanutse ibiro ku buryo butandukanye. Kurugero, mubarwayi bahabwa dosiye ya 4mg, 8mg, na 12mg, 92%, 100%, na 100% byabarwayi, batakaje 5% cyangwa birenga ibiro byabo. Mu bundi bushakashatsi [3] , ibigeragezo bibiri byateganijwe byitabiriwe n’abarwayi 353 barwaye ubwoko bwa 2 metabolism mellitus bwerekanye ko ugereranije na placebo, GLP-3 ishobora kugabanya cyane uburemere bw’umubiri w’abarwayi ku gipimo cya 11.89, kandi ikanagabanya na gemoglobine (HbA1C). Byongeye kandi, mu bigeragezo by’abarwayi bakuze bafite umubyibuho ukabije nta metabolisme, 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 mellitus: GLP-3 irerekana kandi ubushobozi bumwe na bumwe bwo kuvura ubwoko bwa 2 metabolism mellitus. Mu bigeragezo bimwe na bimwe by’amavuriro, GLP-3 yerekanye ko igabanuka rya gemoglobine glycated (HbA1c) no kugabanya ibiro biterwa no kugabanuka. Kurugero, mubushakashatsi bumwe, mubarwayi bafite metabolism yo mu bwoko bwa 2, GLP-3 yerekanye ingaruka zikomeye zo kurwanya glucose. Ugereranije na platbo, glycated hemoglobine yagabanutseho 1,64% [3] . Byongeye kandi, mu buryo butemewe, buhumye-buhumyi, umwanya wawo kandi bugenzurwa n’ibikorwa bigereranywa n’itsinda rya 2, icyitegererezo cy’inyamanswa zifite ubwoko bwa 2 metabolism mellitus, nyuma yo guhabwa imiti ya GLP-3, cyerekanye ko igabanuka rikabije ry’imisemburo ya gemoglobine, kandi uburemere bw’umubiri nabwo bwaragabanutse ku buryo buterwa na dose [4] . Ibi birashobora guterwa ningaruka zuzuye zibiyobyabwenge kuri GLP-1, GCGR, na GIPR, bitezimbere glucose metabolism hamwe nuburinganire bwingufu.
Kunoza ibintu bishobora gutera umutima-mitsi: GLP-3 ntishobora kugabanya ibiro byumubiri gusa ahubwo inateza imbere ingaruka ziterwa numutima nimiyoboro yumutima, nka serumu ya lipide ya serumu hamwe na glycated hemoglobine. Ibi byerekana isano iri hagati yumubyibuho ukabije nindwara zifata umutima, kandi GLP-3 irashobora guteza imbere ubuzima bwimitsi yumutima 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 glucose yamaraso kubarwayi bafite metabolisme, bityo bikagabanya ibyago byindwara z'umutima n'imitsi [3, 5, 6].
Kuvura indwara zumwijima zidafite inzoga (NAFLD): GLP-3 nigitabo gishya cyakira reseptor agonist peptide yibasira reseptor ya glucagon (GCGR), glucose-iterwa na insulineotropic polypeptide reseptor (GIPR), hamwe na glucagon isa na 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 bwakozwe mu byumweru 48 ku bitabiriye amahugurwa bafite indwara ziterwa n’umwijima ziterwa n’umwijima hamwe n’ibinure by’umwijima bingana na ≥10%. Ibisubizo byerekanye ko mu byumweru 24, impuzandengo ugereranije n’amavuta y’umwijima uhereye ku murongo fatizo 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 bari + 0.3% [7] . 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 kugenga metabolisme yumuntu kuva mubice byinshi ikora reseptor ya glucagon, reseptor ya glucose iterwa na glucose, na reseptor ya peptide-1 ya reseptor, kunoza igenzura rya glucose yamaraso, kugabanya ibiro byumubiri, no kugenzura metabolisme ya lipide. Kugaragara kwa GLP-3 byazanye uburyo bushya bwo kuvura abarwayi bafite umubyibuho ukabije, ubwoko bwa 2 metabolism mellitus, n'ibindi.
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].
