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▎ Imiterere ya GLP-2
Inkomoko: PubChem |
Urukurikirane: Tyr- {Aib} -Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile- {Aib} -Leu-Asp-Lys-Ile-Ala-Gln- {diacid-C20-gamm a-Glu- (AEEA) 2-Lys} -Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Inzira ya molekulari: C 225H 348N 48O.68 Uburemere bwa molekuline: 4813 g / mol Numero ya CAS: 2023788-19-2 PubChem CID: 163285897 Synonyme: Zepbound; Mounjaro |
G GLP-2 Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na GLP-2?
GLP-2 nibiyobyabwenge bya polypeptide. Ubushakashatsi niterambere ryayo bituruka ku gusobanukirwa byimazeyo aho ubushobozi bwa GLP-1 bwakira reseptor agonist mu kuvura metabolism yo mu bwoko bwa 2 n'umubyibuho ukabije muri kiriya gihe. Nubwo agoniste ya GLP-1 yerekanye imikorere myiza mugucunga glucose yamaraso no kugabanya ibiro, abahanga basanze imikorere yabo ya reseptor ya GIP idakomeye, ibyo bikaba bigabanya imikorere yibiyobyabwenge kurwego runaka. Niyo mpamvu, itsinda ry’ubushakashatsi n’iterambere ryiyemeje guteza imbere imiti mishya ishobora gukora icyarimwe GIPR na GLP-1R icyarimwe kugirango igere ku buryo bunoze kandi bunoze bwo kugenzura amaraso glucose no gucunga ibiro [1].
Mugihe cyubushakashatsi niterambere rya GLP-2, abahanga bakoze ubushakashatsi bwinshi bwibanze nubushakashatsi bwamavuriro. Mubyiciro byubushakashatsi bwibanze, ubushakashatsi bwinyamaswa bwakoreshejwe mugusuzuma neza imiterere ya farumasi ya GLP-2. Ibisubizo byemeje ubushobozi bwayo mu kugenzura amaraso glucose no kugabanya ibiro, bishyiraho urufatiro rwo kwipimisha kwa muganga. Nyuma, GLP-2 yinjiye mu cyiciro cyo kugerageza, harimo icyiciro cya I, II, na III. Icyiciro cya mbere cyasuzumye cyane cyane umutekano, kwihanganira, hamwe n’imiti ya farumasi, kandi ibisubizo byagaragaje umutekano mwiza no kwihanganira. Icyiciro cya II cyongeye gukora ubushakashatsi ku mikorere n’umutekano bya dosiye zitandukanye ku barwayi bafite metabolism yo mu bwoko bwa 2, mbere yo kumenya urugero rwiza. Icyiciro cyingenzi cya III ibizamini byamavuriro, nka SURPASS yubushakashatsi, bwarimo umubare munini wabarwayi bafite metabolism yo mu bwoko bwa 2. Ibisubizo byagaragaje ko GLP-2 yarutaga cyane GLP-1 yakira reseptor agoniste, nka GLP-1, mu kugabanya glucose yamaraso nuburemere, bitanga ibimenyetso bifatika byerekana ibicuruzwa [1].
GLP-2 ni polypeptide igizwe na acide 39 amine, kandi imiterere yarahinduwe kugirango iteze imbere na farumasi. Igishushanyo cyacyo cyihariye cyububasha gishobora kwinjiza ingaruka za incretine ebyiri, GIP na GLP-1, muri molekile imwe, igakora imisemburo ya hormone igira uruhare mukurwanya glucose yamaraso hakoreshejwe uburyo bubiri. By'umwihariko, kuruhande rumwe, ikora kuri pancreas kugirango iteze imbere insuline kandi ibuza glucagon kurekura glucose yamaraso; kurundi ruhande, ikora kuri sisitemu yo hagati yububiko, gutinda gusiba gastrica, kongera guhaga, kugabanya ubushake bwo kurya no gufata ibiryo, no kugera kubicunga ibiro. Ubu buryo bubiri butanga GLP-2 inyungu zidasanzwe mu kuvura metabolism yo mu bwoko bwa 2 n'umubyibuho ukabije, bigaha abarwayi uburyo bunoze bwo kuvura [1].
Ni ubuhe buryo bwo gukora bwa GLP-2?
GLP-2 igabanya glucose yamaraso ikoresheje uburyo bwinshi bukurikira:
Gukora kwa GLP-1: GLP-2 ihuza reseptor ya GLP-1 kuri selile beta pancreatic beta, bigana ibikorwa bya GLP-1 bisanzwe. GLP-1 ni imisemburo ikorwa n amara ningirakamaro mukubungabunga glucose homeostasis. Irashobora guteza insimburangingo ya insuline, gusohora, hamwe no kumva glucose, no kugabanya ururenda rwa glucagon kugirango itere guhaga no guhagarika ubushake bwo kurya. Ku barwayi bafite metabolisme yo mu bwoko bwa 2, insuline idahagije cyangwa igabanya ubukana bwa insuline itera glucose yamaraso. GLP-2 yongera imisemburo ya insuline ikora reseptor ya GLP-1, igateza imbere glucose yamaraso. Muri icyo gihe, ibikorwa bya reseptor ya GLP-1 birashobora kandi kubuza irekurwa rya glucagon, bikagabanya inkomoko ya glucose yamaraso kandi bikagira uruhare mu kugenzura glucose yamaraso [2].
Gukora kwa GIP yakira: GLP-2 ikora kubakira GIP, kandi kuyikora birashobora kongera insuline no gusohora. GIP yakira igaragara cyane mubice nka pancreatic beta selile. Nyuma yo gukora, binyuze mumyanya ndangagitsina yerekana inzira, insuline isohoka, kandi selile yitabira insuline, bikagabanya glucose yamaraso neza [2] . Izi ngaruka ebyiri za reseptor agonist zituma GLP-2 ikora neza kuruta GLP-1 yakira reseptor agonist mugutezimbere insuline no kubuza glucagon gusohora [2].
Gutinda Gusohora Gastrici no Kongera Guhaza: GLP-2 irashobora gutinza ubusa gastrica, ikongerera igihe cyo gutura ibiryo mu gifu, igabanya umuvuduko wintungamubiri zintungamubiri, kandi ikarinda kwiyongera gukabije kwa glucose yamaraso nyuma yinyuma. Ingaruka zayo mu gusiba gastrica iragereranywa nki GLP-1 reseptor agonist. Muri icyo gihe kandi, ikora kuri sisitemu yo hagati yo hagati, ikongera guhaga, igabanya ubushake bwo kurya no gufata ibiryo, ibyo bikaba bikwiranye cyane cyane n’ikibazo cy’umubyibuho ukabije gikunze guherekezwa n’abarwayi bafite metabolism yo mu bwoko bwa 2, bifasha kunoza insuline ndetse n’imiterere rusange ya metabolike [2].
Kunoza ibyiyumvo bya insuline na Diyabete ya Lipide: GLP-2 irashobora kongera urwego rwa adiponectine, adipocytokine ijyanye no kumva insuline, igafasha kunoza insuline, bigatuma selile zifata neza kandi zigakoresha glucose, no kugabanya glucose yamaraso (Anonymous, 2023). Byongeye kandi, irashobora kandi kunoza imiterere ya lipid, ikagira ingaruka zo gukingira ubuzima bwumutima. Byaragaragaye ko ishobora kuzamura umuvuduko w'amaraso, kugabanya cholesterol ya LDL na triglyceride [3].
Inkomoko: PubMed [5]
Ni ubuhe bushakashatsi bujyanye?
Ingaruka zo gucunga ibiro ku barwayi bafite umubyibuho ukabije na Diyabete yo mu bwoko bwa 2
Ubushakashatsi bwinshi bw’amavuriro bwemeje ko GLP-2 igira ingaruka zikomeye zo kugabanya ibiro. Mu bushakashatsi bwa 'SURMOUNT-2 ', iki cyiciro cya 3, impumyi ebyiri, impumyi, igenzurwa na platbo yakorewe mu bihugu birindwi. Abakuze (bafite imyaka 18 ans) bafite BMI ya 27 kg / m² cyangwa hejuru na HbA₁c ya 7 - 10% bariyandikishije kandi bahabwa amahirwe yo kwakira inshuro imwe mucyumweru inshinge ya GLP-2 (10 mg cyangwa 15 mg) cyangwa umwanya wa byumweru 72. Ibisubizo byerekanye ko ku cyumweru cya 72, ijanisha ryo kugabanuka ibiro muri GLP-2 10 mg na 15 mg byari -12.8% na -14.7%, ugereranije na -3.2% mumatsinda yabobo. Ikigereranyo cyo kuvura cya GLP-2 10 mg na mg 15 ugereranije na placebo cyari -9,6 ku ijana na -11,6 ku ijana, byari bifite imibare (p <0.0001). Byongeye kandi, abarwayi benshi bahabwa imiti ya GLP-2 bageze ku gipimo cyo kugabanya ibiro 5% cyangwa byinshi (79 - 83% vs 32%) (Garvey WT, 2023). Muri ubu bushakashatsi, impuzandengo y'ibiro fatizo yari kg 100.7, BMI yari 36.1 kg / m², naho HbA₁c yari 8.02%. Nyuma yibyumweru 72 bivurwa, GLP-2 ntabwo yagabanije cyane ibiro byumubiri gusa ahubwo yanagize ingaruka nziza mugucunga glucose yamaraso [4].
Gutezimbere Neuropathie Diyabete
Ubushakashatsi bwerekanye ko GLP1-RAs ishobora kugabanya ibyago byo guta umutwe ku barwayi bafite metabolism yo mu bwoko bwa 2 mu kunoza kwibuka, kwiga, no gutsinda ubumuga bwo kutamenya. Nka GIP-RA / GLP-1RA ebyiri, mumurongo w'akagari ka neuroblastoma (SHSY5Y), ubushakashatsi bwerekanye ko GLP-2 igira ingaruka ku bimenyetso byerekana imikurire ya neuronal (CREB na BDNF), apoptose (igipimo cya BAX / Bcl2), itandukaniro (pAkt, MAP2, GAP43, na AGBL4, GLUT, GLUT1) Ibisubizo byibanda ku ruhare rwa GLP-2 mu gukora inzira ya pAkt / CREB / BDNF no kumanuka werekana kaskade hamwe na neuroprotective efficacy, byerekana ko ishobora kurwanya ingaruka ziterwa na hyperglycemia hamwe no kurwanya insuline kurwego rwa neuronal. Kubwibyo, GLP-2 irashobora kunoza imitekerereze ya neurodegeneration iterwa na hyperglycemia kandi ikanesha insuline irwanya insuline, igatanga ubumenyi bushya bwo kunoza imitekerereze ya metabolism iterwa na metabolism [5].
Iterambere ryubushakashatsi mukuvura Diyabete yo mu bwoko bwa 2
Nubwoko bushya bwibiyobyabwenge bya hypoglycemic, GLP-2 ibaye agoniste ya mbere ya GIP / GLP-1R yemewe yo kuvura metabolism muri Amerika. Ibigeragezo byinshi binini byamavuriro byemeje ko glucose igabanuka cyane ningaruka zo kugabanya ibiro, kandi ifite ubushobozi bwo kurinda umutima. Igitekerezo cya peptide ya syntetique yafunguye ibintu byinshi bitazwi kuri GLP-2. Ibigeragezo bikomeje (NCT04166773) nibimenyetso byerekana ko ari imiti itanga icyizere mubijyanye nindwara zumwijima zidafite inzoga (NAFLD), impyiko na neuroprotection [6] (Ma Z, 2023).
Ingaruka ndende za GLP-2 kubuzima bwumutima
GLP-2 irashobora kugabanya ibyago byindwara zifata umutima nimiyoboro itera kugabanya ibiro. Ubushakashatsi bwasuzumye ingaruka GLP-2 igira ku mubyibuho ukabije n'indwara z'umutima n'imitsi ku bantu bakuze b'Abanyamerika [7] . Ubushakashatsi bwerekanye ko mu bantu bakuze b'Abanyamerika bemerewe kuvurwa GLP-2, nyuma yo kuvurwa hamwe na mg 15 za GLP-2, abagera kuri 70,6% na 56.7% by'abantu bakuru batakaje ≥ 15% na ≥ 20% by'uburemere bw'umubiri, bivuze ko umubare wa 58.8% ugabanuka. Mu badafite indwara z'umutima n'imitsi, bivugwa ko imyaka 10 y’indwara zifata umutima n’umutima zaragabanutse ziva kuri 10.1% 'mbere yo kuvurwa ' zigera kuri 7.7% 'nyuma yo kuvurwa ', ibyago byagabanutseho 2,4% naho ibyago bigereranywa na 23,6%, bikumira miliyoni 2 z’indwara zifata umutima.
Mu gusoza, GLP-2 ni ubwoko bushya bwa agonist ya kabiri ya reseptor ya GIP na GLP-1, bifite akamaro kanini mukuvura metabolism yo mu bwoko bwa 2 n'umubyibuho ukabije. Irashobora guteza imbere neza gusohora kwa insuline, ikabuza gusohora glucagon, kugenzura neza glucose yamaraso, kugabanya ibyago byingaruka, kunoza imikorere ya selile beta pancreatic beta, gutinza iterambere rya metabolism, kandi ikagira ingaruka kumutima. Mu kuvura umubyibuho ukabije, irashobora kugabanya neza gufata ibiryo, ubushake buke, kongera guhaga, gufasha abarwayi bafite umubyibuho ukabije guta ibiro, no kugabanya ibyago by’ingaruka ziterwa n'umubyibuho ukabije. Irashobora kandi kunoza insuline irwanya no guhinduranya lipide. Byongeye kandi, irerekana ubushobozi mukuvura indwara zidasanzwe ziterwa na metabolike nka steatohepatite itari inzoga, syndrome de apnea, no kunanirwa k'umutima, kandi irashobora icyarimwe kunoza ibipimo byinshi bya metabolike, itanga gahunda yuzuye yo kuvura. Uburyo bwayo bwo gutera inshuro imwe mucyumweru biroroshye gukoresha kandi birashobora kunoza uburyo bwo kuvura abarwayi. Mugucunga neza glucose yamaraso nuburemere no kugabanya ibyago byingaruka, birashobora guteza imbere cyane abarwayi kumubiri, bikongera ubushobozi bwibikorwa byabo bya buri munsi nubuzima bwiza, bikongerera icyizere cyo kurwanya indwara, kugabanya imitekerereze yabo, no kunoza imibereho yabo.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Dr. William T. Garvey ni intiti n’umushakashatsi uzwi cyane bifitanye isano n’ibigo byinshi bizwi, birimo kaminuza ya Alabama i Birmingham, kaminuza ya Aston, n’ikigo nderabuzima cya Birmingham. Amashuri ye n'uburambe bw'umwuga bikubiyemo amasomo atandukanye mu buvuzi na siyansi. Dr. Garvey yagize uruhare runini mu bijyanye na endocrinology na metabolism, imirire n’imirire, ibinyabuzima na biyolojiya y’ibinyabuzima, ndetse n’ubuvuzi rusange ndetse n’imbere, yibanda cyane kuri sisitemu yumutima nimiyoboro y’umutima. Ibikorwa bye byamenyekanye cyane kandi byubahwa, cyane cyane byiswe Umushakashatsi wavuzwe cyane mu cyiciro cyambukiranya imipaka mu myaka ya 2023 na 2024, byerekana ingaruka n’ingaruka z’ubushakashatsi bwe ku muryango mugari wa siyansi.
Ubushakashatsi bwa Dr. Garvey n'ubuhanga bugera no mu bice bitandukanye by'indwara ziterwa na metabolike. Yagize uruhare runini mu kwiga metabolism mellitus, umubyibuho ukabije, hamwe n’ibibazo bifitanye isano nayo, agamije kuvumbura ingamba zo kuvura udushya no kunoza umusaruro w’abarwayi. Ibikorwa bye bikubiyemo ubushakashatsi bwibanze bwa siyansi, ibizamini by’amavuriro, n’ubushakashatsi bw’ubuhinduzi, bikuraho itandukaniro riri hagati y’ibyavuye muri laboratoire hamwe n’ubuvuzi busanzwe ku isi. Binyuze mu bushakashatsi bwe bwimbitse, Dr. Garvey yagize uruhare mu gusobanukirwa byimbitse n’uburyo bw’imiterere y’imihindagurikire y’imihindagurikire y’imiterere kandi yafashije mu gushyiraho umurongo ngenderwaho w’amavuriro na protocole y’ubuvuzi mu bijyanye na endocrinology na metabolism. Dr. William T. Garvey yanditse ku rutonde rw'ibisobanuro byatanzwe [4 ].
