Retatrutid (GLP-3) 10mg

▎ Imiterere ya GLP-3

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GLP-3 (LY3437943) ni peptide yiperereza isobanurwa nkumuntu wakira reseptor agoniste inshuro eshatu kuri reseptor ya glucagon imeze nka peptide-1 (GLP-1R), reseptor ya glucose iterwa na insulineotropique polypeptide (GIPR), na reseptor ya glucagon (GCGR). [1,2]

Igishushanyo1. Igishushanyo cyerekana inzira eshatu zakira zaganiriweho kuri GLP-3 mu isubiramo ryavuzwe.

Iterambere ry'ubushakashatsi

Coskun, Tamer, na bagenzi be bize GLP-3 muri C57 / Bl6 imirire iterwa n'umubyibuho ukabije (DIO). Abanditsi bavuze ko impinduka zishingiye ku bipimo by’ibiro by’umubiri, gufata kalori, ibigize umubiri, glucose yamaraso, insuline, ALT, na triglyceride yumwijima. Ubushakashatsi bw'inyongera muri ubwo bushakashatsi bwakoreshejwe mu gusuzuma uruhare rwa GCGR, GIPR, na GLP-1R byerekana ibisubizo byagaragaye mbere. [2]

Igishushanyo2. Uburemere bw'umubiri, gufata kalori, ibigize umubiri, hamwe na metabolike iheruka kuvugwa kuri LY3437943 mu mbeba zifite umubyibuho ukabije ziterwa n'imirire.

Imbeba ziterwa n'umubyibuho ukabije zakira rimwe-buri munsi (QD) izamuka rya LY3437943 muminsi 21 mubushakashatsi bwavuzwe.

(A) Guhindura ijanisha ryibiro byumubiri mugihe runaka.

(B) Cumulative calorie gufata igihe.

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(G - J) Ibipimo byubuzima bwa metabolike nyuma yubushakashatsi: glucose yamaraso (G), insuline (H), ALT (I), na triglyceride yumwijima (J).

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Ibyatanzwe bisobanurwa nkibisobanuro ± SEM hamwe n = 6 (A - L). Isesengura mibare muri (C) - (K) ryakozwe hakoreshejwe inzira imwe ya ANOVA n’imodoka, bifite akamaro kasobanuwe kuri p <0.05. < P <0.05, ∗∗ p <0.01, ∗∗∗ p <0.001, ∗∗∗∗ p <0.0001 n’imodoka, p <0.05 na GLP-2. ALT, alanine aminotransferase; LY, LY3437943; SEM, ikosa risanzwe ryerekana. +

Li, Wenzhuo, n'abandi. yakoresheje microscopi ya cryo-electron kugirango isuzume GLP-3 ihujwe na GLP-1R, GIPR, na GCGR. Abanditsi batangaje ko akarere ka N-terminal ka peptide gakorana na reseptor transembrane ihuza umufuka, mu gihe akarere ka C-term gatanga umusanzu mu mikoranire n’uturere twa reseptor zidasanzwe. Ubushakashatsi bwerekanye uburyo bwihariye bwo kwakira no kwakira abantu mu bice bitatu byakira.

Joachim Neumann na bagenzi be basuzumye GLP-3 mu myiteguro y’umuntu yitaruye yabonetse mu gihe cyo kubaga umutima. Abanditsi bavuze ko kwibanda ku gihe no guterwa nigihe cyo guhindura imbaraga kandi bakoresheje antagonist reseptor kugirango bakore iperereza ku ruhare rwa GCGR, GIPR, na GLP-1R. Basabye uburyo bwo kwerekana ibimenyetso bijyanye na cAMP mubihe byubushakashatsi bwakozwe na ex vivo.

Coskun n'abandi. yanatangaje raporo yubushakashatsi bwumutekano wumutima nimiyoboro y'amaraso muri cynomolgus. Mu bushakashatsi bwakozwe inshuro imwe, umuvuduko wumutima wari hejuru kuruta kugenzura icyarimwe nyuma ya LY3437943, hamwe nubushakashatsi bunini butanga kwiyongera cyane. Mu mezi atandatu yisubiramo-yuzuye, umuvuduko ukabije wumutima wagaragaye mugihe cyo kunywa kandi wasobanuwe ko biterwa na dose; haravuzwe kandi impinduka z'umuvuduko w'amaraso wa systolique na diastolique. Izi nyigisho zakozwe mubihe bidasanzwe byo kwiga.

Imipaka ntarengwa

Ubwoko bwinyamanswa zitanga amakuru mubihe byubushakashatsi bwasobanuwe ariko ntibishobora kubyara byimazeyo imiterere yumubiri wabantu. Itandukaniro muri biologiya ya reseptor, imihindagurikire y'ikirere ya neuroendocrine, igihe cyo kumara, hamwe n'ibimenyetso byo hepfo bishobora kugira ingaruka kubisobanuro ku moko. Ibyavuye mu bushakashatsi bwakiriwe, ubushakashatsi ku miterere, ingirabuzimafatizo z’abantu, hamwe n’icyitegererezo cy’inyamaswa bigomba gusobanurwa mu buryo bwakoreshejwe kandi ntibigomba gufatwa nkikimenyetso cy’umutekano w’ubuvuzi cyangwa cyiza. [2,4-6]

COCER Peptide itanga GLP-3 gusa kugirango ikoreshwe muri laboratoire ntabwo ikoreshwa kubantu cyangwa amatungo. Ibikoresho biri kuriyi page byerekana muri make ibyavuye mu bitabo byavuzwe haruguru kandi ntibisobanura ibirego bijyanye n’ubuvuzi, umutekano, gusuzuma, kuvura, gukumira, cyangwa gukoresha abantu.

Imirongo ijyanye

] Ikinyamakuru cyo mu Burayi cya Pharmacology Clinical, 2024,80 (5): 669-676.

DOI: 10.1007 / s00228-024-03646-0

[2] COSKUN T, URVA S, ROELL WC, n'abandi. LY3437943, igitabo cyitwa glucagon inshuro eshatu, GIP, na GLP-1 reseptor agonist yo kurwanya glycemic no kugabanya ibiro: Kuva kuvumburwa kugeza ibimenyetso byubuvuzi byerekana [J]. Diyabete y'utugari, 2022,34 (9): 1234-1247.e9.

DOI: 10.1016 / j.cmet.2022.07.013

[3] LI W, ZHOU Q, CONG Z, n'abandi. Ubushishozi bwuburyo butatu agonism kuri GLP-1R, GIPR na GCGR bugaragazwa na GLP-3 [J]. Kuvumbura Akagari, 2024,10: 77.

DOI: 10.1038 / s41421-024-00700-0

[4] NEUMANN J, AHLREP U, HOFMANN B, n'abandi. Ingaruka za Inotropique ya GLP-3 mu myiteguro y’umuntu yitaruye [J]. Ububiko bwa Naunyn-Schmiedeberg bwa Farumasi, 2026,399 (1): 317-327.

DOI: 10.1007 / s00210-025-04421-3

[5] LUTZ T A. Ubwoko bw’inyamabere bw’indwara ya diyabete, hibandwa kuri diyabete yo mu bwoko bwa 2 [J]. Isuzuma rya Kamere Endocrinology, 2023,19 (6): 350-360.

DOI: 10.1038 / s41574-023-00818-3

[6] TU Q, LIU G, LIU X, n'abandi. Ibitekerezo byo gukoresha primates zitari abantu mubushakashatsi bwa Exposome [J]. Ibidukikije n’umutekano w’ibidukikije, 2024,286: 117199. DOI: 10.1016 / j.ecoenv.2024.117199.

IBICURUZWA BYOSE, INGINGO, IBIKORWA BY'IKORANABUHANGA, IBISOBANURO BY'IBICURUZWA, N'IZINDI MAKURU YATANZWE KURI URU RUBUGA BITEGANYIJWE CYANE KUBUSHAKASHATSI BWA LABORATORY, AMAKURU, N'UBUREZI. 

Ibicuruzwa bitangwa na Cocer Peptides bigenewe gusa mubushakashatsi bwa vitro na laboratoire kandi ntibigenewe gukoreshwa mubantu cyangwa mubuvuzi bwamatungo, kurya abantu, gukoresha amavuriro, gukoresha indwara yo kwisuzumisha, gukoresha imiti, guhuza, kwiyobora, gutera inshinge, cyangwa ubundi buryo ubwo aribwo bwose bwo kuyobora abantu cyangwa inyamaswa. Ibicuruzwa ntabwo bigamije gusuzuma, kuvura, gukiza, kugabanya, cyangwa gukumira indwara iyo ari yo yose cyangwa ubuvuzi, nta nubwo bigamije kugira ingaruka ku miterere cyangwa imikorere y’umubiri w’umuntu cyangwa inyamaswa. Keretse niba byavuzwe ukundi, ibicuruzwa bitangwa kururu rubuga ntabwo byigeze bisuzumwa cyangwa ngo byemezwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA) kugira ngo gikoreshe abantu cyangwa amatungo. Ibivugwa byose kubushakashatsi bwatangajwe, inzira ya biohimiki, inzira ya molekuline, cyangwa ubushakashatsi bwakozwe butangwa gusa kubiganiro bya siyansi nubushakashatsi bugamije kandi ntabwo bigize inama zubuvuzi, ibirego byo kuvura, kubayobora, cyangwa amabwiriza yo gukoresha. Abaguzi bafite inshingano zo kureba niba ibicuruzwa byose byabonetse, bigakorwa, bikabikwa, bikoreshwa, kandi bikajugunywa hakurikijwe amategeko, amabwiriza, ibisabwa mu nzego, hamwe n’umutekano wa laboratoire.