G GLP-2 Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na GLP-2?
Iterambere rya GLP-2, imiti ya polypeptide ikora, yaturutse ku kumenya aho ubushobozi bwa GLP-1 bwakira reseptor agonist mu kuvura metabolism yo mu bwoko bwa 2 n'umubyibuho ukabije. Nubwo GLP-1 yakira agoniste ikora neza mugucunga amaraso glucose no kugabanya ibiro, abahanga basanze imikorere yabo idahwitse ya reseptor ya GIP itagira ingaruka mbi zo kuvura. Niyo mpamvu, amatsinda yubushakashatsi yari agamije guteza imbere imiti mishya ishoboye gukora GIPR na GLP-1R kugirango igenzure neza glycemic no gucunga ibiro [1].
Ibigeragezo byinshi byubuvuzi nubuvuzi byakozwe mugihe cyiterambere.
Ubushakashatsi bwibanze bwinyamanswa bwasuzumye imiti ya farumasi, yemeza ko ifite ubushobozi bwo kurwanya glycemic no kugabanya ibiro. Icyiciro cya mbere cyamavuriro cyasuzumye cyane cyane umutekano, kwihanganira, hamwe na farumasi, byerekana umutekano mwiza
no kwihanganira. Icyiciro cya II cyakomeje gukora ubushakashatsi ku mikorere n’umutekano ku kigero gitandukanye cy’abarwayi ba metabolisme yo mu bwoko bwa 2, mbere yo kumenya ibipimo bifatika. Igeragezwa rya Pivotal Icyiciro cya III nkurukurikirane rwa SURPASS, rurimo amatsinda manini y’abarwayi ba metabolism yo mu bwoko bwa 2, ryerekanye ko GLP-2 yarushije cyane GLP-1 reseptor agoniste mu kugabanya glucose yamaraso nuburemere, itanga ibimenyetso bifatika byerekana ibicuruzwa [1].
Igizwe na acide 39 amine ihindura imiterere kugirango iteze imbere kandi ikore neza, imiterere yihariye ihuza ibikorwa bya GIP na GLP-1 muri molekile imwe, ikora imisemburo ya hormone igira uruhare mukurwanya glycemic hakoreshejwe uburyo bubiri.
Ku ruhande rumwe, ikora kuri pancreas kugirango iteze imbere insuline kandi ibuza glucagon kurekura glucose igabanya amaraso; kurundi ruhande, ikora kuri sisitemu yo hagati yo gutinda gusiba gastric, kongera guhaga, no kugabanya ubushake bwo kurya no gufata ibiryo byo gucunga 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:
Gukora kwa GLP-1 Kwakira: Guhambira reseptor ya GLP-1 kuri selile pancreatic β selile, bigana GLP-1 karemano kugirango iteze insimburangingo ya insuline, isohoka, hamwe na glucose sensibilisation mugihe igabanya glucagon kugirango yongere guhaga no guhagarika ubushake bwo kurya. Mu barwayi ba metabolism yo mu bwoko bwa 2, gukora reseptor ya GLP-1 byongera imisemburo ya insuline kugirango irusheho kurwanya glycemic, mugihe kubuza glucagon kurekura bigabanya amasoko ya glucose yamaraso, bifasha kugenga glycemic [2].
Gukora kwa GIP yakira: Gukora kuri reseptor ya GIP, gukora byongera insuline no gusohora. GIP yakira cyane cyane mubice nka selile pancreatic β selile, kandi gukora binyuze munzira zerekana ibimenyetso byongera insuline kandi bikanonosora insuline kugirango insuline igabanuke neza mumaraso [2] . Ubu buryo bubiri bwa reseptor agonism butuma GLP-2 ikora neza mugutezimbere imisemburo ya insuline no kubuza glucagon gusohora kuruta GLP-1 yakira reseptor agonist [2] .
Gutinda Gastrici Gutinda no Kwihaza Byinshi: Itinda gusiba gastrica, kongera igihe cyo kugaburira ibiryo mu gifu kugirango igabanye intungamubiri kandi irinde glucose yamaraso nyuma yinyuma. Hagati aho, gukora kuri sisitemu yo hagati yo kongera ibyokurya bigabanya ubushake bwo kurya no gufata ibiryo, cyane cyane bifasha umubyibuho ukabije akenshi bifitanye isano na metabolism yo mu bwoko bwa 2, bifasha mukurwanya insuline no guhindagurika muri rusange [3].
Kunoza ibyiyumvo bya insuline hamwe na Diyabete ya Lipide: Kuzamura urugero rwa adiponectine - ibintu binini byamavuta bifitanye isano no kumva insuline - bifasha kunoza insuline, bigatuma selile zifata neza kandi zigakoresha glucose kugirango glucose igabanuke [2] (Anonymous, 2023). Itezimbere kandi imyirondoro ya lipide, hamwe ningaruka zishobora gukingira ubuzima bwumutima nimiyoboro yimitsi, imaze kugaragara ko izamura umuvuduko wamaraso no kugabanya cholesterol ya LDL na triglyceride [3].
Ni ubuhe bushakashatsi bufite akamaro?
GLP-2 yerekana imbaraga zikomeye mugucunga ibiro kubarwayi bafite umubyibuho ukabije nubwoko bwa 2. Mu bushakashatsi bwa SURMOUNT-2, icyiciro cya 3, impumyi ebyiri, zidahwitse, zagenzuwe na platbo zakozwe mu bihugu birindwi, abantu bakuru bafite imyaka 18 na BMI kg27 kg / m² na HbA1c 7-10% byatoranijwe kugirango bakire buri cyumweru munsi ya GLP-2 (10 mg cyangwa 15 mg) cyangwa umwanya wa byumweru 72. Mugihe cyicyumweru cya 72, ijanisha ryo kugabanya ibiro byari .8 12.8% na 14.7% muri GLP-2 10 mg na 15 mg hamwe na 15 mg na −3.2% mumatsinda ya placebo, hamwe nibigereranyo bivura bivura −9.6 na 11,6% ugereranije na placebo (p <0.0001). Byongeye kandi, abarwayi benshi bavuwe na GLP-2 bageze ku kugabanya ibiro 5% (79-83% na 32%) (Garvey WT, 2023). Hamwe na baseline bivuze uburemere 100.7 kg, BMI 36.1 kg / m², na HbA1c 8.02%, ibyumweru 72 byo kuvura hamwe na GLP-2 ntabwo byagabanije cyane ibiro ahubwo byanateje imbere kurwanya glycemic [4] .
Mu kunoza imitekerereze ya neuropathie ijyanye na metabolism, ubushakashatsi bwerekana ko GLP1-RAs ishobora kugabanya ibyago byo guta umutwe ku barwayi ba metabolism yo mu bwoko bwa 2 mu kunoza kwibuka, kwiga, no gutsinda ubumuga bwo kutamenya. Nka GIP-RA / GLP-1RA ebyiri, GLP-2 yizewe mumirongo ya selile ya neuroblastoma (SHSY5Y) kubera ingaruka zayo kumikurire ya neuronal (CREB na BDNF), apoptose (igipimo cya BAX / Bcl2), itandukaniro (pAkt, MAP2, GAP43, na AGBL4), hamwe na insuline (GLUT1, GLUT1). Byagaragaye ko bigira ingaruka kuri neuroprotective mugukoresha inzira ya pAkt / CREB / BDNF hamwe no kumanuka werekana kasake, kurwanya hyperglycemia- na insuline ziterwa na insuline kurwego rwa neuronal. Rero, GLP-2 irashobora guteza imbere hyperglycemia iterwa na neurodegeneration kandi ikanesha insuline irwanya insuline, igatanga ubumenyi bushya bwo gucunga neuropathie iterwa na metabolism ..
Mu bwoko bwa 2 bwo kuvura metabolism, GLP-2, imiti ya hypoglycemic, yabaye iyambere yemewe ya GIP / GLP-1R agonist ya metabolisme muri Amerika Ibigeragezo byinshi binini by’amavuriro byemeza ingaruka zikomeye zo kugabanya glycemique no kugabanya ibiro, hamwe n’ubushobozi bwo kurinda umutima. Igitekerezo cya peptide ya syntetique yafunguye ibintu byinshi bitashakishijwe kuri GLP-2. Ibigeragezo n'ibimenyetso bikomeje byerekana ko ari umuti utanga ikizere ku ndwara z’umwijima zidafite inzoga (NAFLD), kurinda impyiko, na neuroprotection [6].
Ku bijyanye n'ingaruka z'igihe kirekire ku buzima bw'umutima n'imitsi, GLP-2 irashobora kugabanya indwara z'umutima n'imitsi (CVD) mu guteza imbere kugabanya ibiro. Ubushakashatsi bwakozwe ku ngaruka GLP-2 yagize ku mubyibuho ukabije ndetse na CVD ku bantu bakuze bo muri Amerika bwerekanye ko mu bemerewe kwivuza GLP-2, ubuvuzi bwa mg 15 bwagereranijwe kugera ku gipimo cya ≥15% na ≥20% mu kugabanya ibiro 70,6% na 56.7% by’abantu bakuru, bivuze ko kugabanuka kwa 58.8%. Ku bantu badafite CVD, ibyago bivugwa ko imyaka 10 ya CVD yagabanutse kuva kuri 10.1% 'mbere yo kuvurwa ' igera kuri 7.7% 'nyuma yo kuvurwa, ' byerekana ko ingaruka zagabanutseho 2,4% naho kugabanuka kwa 23,6%, bikaba bishobora gukumira miliyoni 2 zanduye CVD [7].
Umwanzuro
Muri make, GLP-2 nigitabo gishya cya agonist ya reseptor ya GIP na GLP-1, gifite akamaro kanini mukuvura metabolism yo mu bwoko bwa 2 n'umubyibuho ukabije. Itera imbere cyane gusohora insuline, ikabuza gusohora glucagon, kandi ikagenga neza glucose yamaraso, kugabanya ingaruka ziterwa no kunoza imikorere ya pancreatic β-selile no kudindiza iterambere rya metabolism, hamwe ningaruka z'umutima. Mu kuvura umubyibuho ukabije, bigabanya neza gufata ibiryo, bigabanya ubushake bwo kurya, byongera guhaga, bifasha kugabanya ibiro, kandi bigabanya ingaruka ziterwa n’umubyibuho ukabije mu gihe biteza imbere insuline na metabolisme ya lipide. Byongeye kandi, irerekana ubushobozi bwo kuvura indwara ziterwa na metabolike nka steatohepatite itari inzoga, syndrome de apnea, hamwe no kunanirwa k'umutima, itanga ubuvuzi bwuzuye mugutezimbere ibipimo byinshi. Gahunda yayo yo gutera inshuro imwe mucyumweru yongerera ubworoherane no kubahiriza abarwayi. Mugucunga neza glucose yamaraso nuburemere, kugabanya ingaruka ziterwa ningorabahizi, no kuzamura cyane imiterere yumubiri, ibikorwa bya buri munsi, nubuzima bwiza, GLP-2 yongerera abarwayi icyizere cyo gucunga indwara, igabanya imitwaro yimitekerereze, kandi ikanahuza n'imibereho.
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'ibitekerezo [4].
