Retatrutid (GLP-3) 10 mg

▎ Ọdịdị GLP-3

▎ Ihe ndabere nke Molecular

GLP-3 (LY3437943) bụ peptide nyocha nke akọwara dị ka agonist nnabata atọ na glucagon-like peptide-1 receptor (GLP-1R), glucose-based insulinotropic polypeptide receptor (GIPR), na glucagon receptor (GCGR).

Fig1. Ngosipụta atụmatụ nke ụzọ nnabata atọ a tụlere maka GLP-3 na nyocha a kpọtụrụ aha.[1]

Ọganihu nyocha

Coskun, Tamer, na ndị ọrụ ibe gụrụ GLP-3 na oke oke ibu nke C57/Bl6 na-ebute oke nri (DIO). Ndị na-ede akwụkwọ kọrọ mgbanwe na-adabere na dose na ịdị arọ ahụ, oriri calorie, nhazi ahụ, glucose ọbara, insulin, ALT, na triglycerides imeju. A na-eji nnwale ndị ọzọ n'otu ọmụmụ ihe ahụ nyochaa ntinye aka nke GCGR, GIPR, na GLP-1R na nzaghachi ndị a na-ahụ anya.[2]

Fig2. Ibu ahụ dị arọ, oriri calorie, nhazi ahụ, na njedebe metabolic kọrọ maka LY3437943 n'ime oke oke ibu na-ebute nri.[2]

Oke oke ibu na-eri nri na-enweta otu ugboro kwa ụbọchị (QD) na-arịgo doses nke LY3437943 maka ụbọchị 21 n'ime ọmụmụ a kpọtụrụ aha.

(A) Mgbanwe na pasentị arọ ahụ ka oge na-aga.

(B) Nchịkọta kalori na-eri n'ime oge.

(C - F) Nhazi ahụ na-agbanwe na gram na njedebe nke ọmụmụ ihe: ịdị arọ (C), oke abụba (D), lean mass (E), na lean / fat mass ratio (F).

(G - J) Usoro ahụike metabolic na njedebe nke ọmụmụ: glucose ọbara (G), insulin (H), ALT (I), na triglycerides imeju (J).

(K) Tụnyere LY3437943 na GLP-2 na usoro ọmụmụ akọwapụtara maka mgbanwe pasentị na ịdị arọ ahụ ka oge na-aga.

(L) Tụnyere LY3437943 na GLP-2 na usoro ọmụmụ akọwapụtara maka oriri calorie ka oge na-aga.

A na-akọwapụta data dị ka ± SEM na n = 6 (A - L). A na-eme nyocha ọnụ ọgụgụ na (C) - (K) site na iji otu ụzọ ANOVA megide ụgbọ ala, nke akọwapụtara na p <0.05. ∗ p <0.05, ∗∗ p <0.01, ∗∗∗ p <0.001, ∗∗∗∗ p <0.0001 na ụgbọ ala, p <0.05 megide GLP-2. ALT, alanine aminotransferase; LY, LY3437943; SEM, njehie ọkọlọtọ nke ihe ọ pụtara.+

Li, Wenzhou, et al. ejiri microscopy cryo-electron nyochaa GLP-3 jikọtara na GLP-1R, GIPR na GCGR. Ndị na-ede akwụkwọ kwuru na mpaghara N-terminal nke peptide na-emekọrịta ihe na akpa akpa transmembrane nke na-anabata ya, ebe mpaghara C-terminal na-enye aka na mmekọrịta na mpaghara ndị na-anabata ihe ọzọ. Ọmụmụ ihe a chọpụtara ma kọntaktị echekwara na nke anabatara n'ofe ogige nnabata atọ ahụ.[3]

Joachim Neumann na ndị ọrụ ibe nyochara GLP-3 na nkwadebe atrial aka nri mmadụ dịpụrụ adịpụ enwetara n'oge ịwa ahụ obi. Ndị ode akwụkwọ kọrọ mgbanwe nleba anya na oge dabere na ike nke nkwekọrịta wee jiri ndị na-emegide ndị na-anabata nnabata mee nyocha itinye aka nke GCGR, GIPR na GLP-1R. Ha tụpụtara usoro nrịbama metụtara cAMP n'okpuru ọnọdụ nke ọmụmụ ex vivo a.[4]

Coskun et al. kọkwara akụkọ nchekwa nchekwa obi na-abụghị nke ahụike na enwe cynomolgus. N'ime nyocha otu dose, ọnụọgụ obi dị elu karịa njikwa oge mgbe LY3437943 ekpughere, yana nnukwu ọmụmụ ihe na-ebute mmụba dị ukwuu. N'ime nyocha nke ọnwa isii na-emegharị ugboro ugboro, a na-ahụ ọnụ ọgụgụ obi dị elu n'oge usoro dose ma kọwaa ya dị ka dose-dabere; A kọkwara mgbanwe na systolic na ọbara mgbali diastolic.[2] Emepụtara nlebanya ndị a n'okpuru ọnọdụ ọmụmụ primate nke mmadụ.

Oke nyocha

Ụdị anụmanụ na-enye ozi n'okpuru ọnọdụ nnwale akọwapụtara mana enweghị ike imepụtaghachi mgbagwoju anya nke physiology mmadụ. Ọdịiche dị na bayoloji nnabata, mmegharị neuroendocrine, oge mkpughe, na mgbama mgbada ala nwere ike imetụta ntụgharị asụsụ n'ofe ụdị. Nchọpụta sitere na nyocha ndị nnata, ọmụmụ ihe nhazi, anụ ahụ mmadụ dịpụrụ adịpụ, na ụdị anụmanụ kwesịrị ịkọwa ya n'ime ihe atụ ejiri mee ihe ma ghara ịgwọ ya dị ka ihe akaebe nke nchekwa ahụike ma ọ bụ nrụpụta ọrụ.[2,4-6].

COCER Peptides na-enye GLP-3 naanị maka iji nyocha ụlọ nyocha ọ bụghị maka iji mmadụ ma ọ bụ ọgwụgwọ anụmanụ. Ihe dị na ibe a na-achịkọta nchoputa a kọrọ na akwụkwọ ndị ọzọ e zoro aka na ya ma ọ dịghị ekwu maka ịdị irè ụlọ ọgwụ, nchekwa, nchọpụta, ọgwụgwọ, mgbochi ma ọ bụ ojiji mmadụ ọzọ.

▎ Okwu ndị dị mkpa

[1] KAUR M, MISRA S. Nlebanya nke ọgwụ nyocha GLP-3, onye nnọchi anya agonist atọ nke akwụkwọ akụkọ maka ọgwụgwọ oke ibu[J]. Akwụkwọ akụkọ European nke Clinical Pharmacology, 2024,80 (5): 669-676.

DOI: 10.1007/s00228-024-03646-0

[2] COSKUN T, URVA S, ROELL WC, et al. LY3437943, akwụkwọ akụkọ glucagon triple, GIP, na GLP-1 agonist maka njikwa glycemic na mbelata ibu: Site na nchọpụta ruo na akaebe ụlọ ọgwụ nke echiche [J]. Ọrịa shuga cell, 2022,34 (9): 1234-1247.e9.

DOI:10.1016/j.cmet.2022.07.013

[3] LI W, ZHOU Q, CONG Z, et al. Nghọta n'usoro n'ime ihe mgbu atọ na GLP-1R, GIPR na GCGR gosipụtara site na GLP-3[J]. Nchọpụta mkpụrụ ndụ, 2024,10:77 .

DOI: 10.1038/s41421-024-00700-0

[4] NEUMMAN J, AHLREP U, HOFMANN B, et al. Mmetụta inotropic nke GLP-3 na nkwadebe atrial mmadụ dịpụrụ adịpụ[J]. Ihe ndekọ nke Naunyn-Schmiedeberg's Archives of Pharmacology, 2026,399(1):317-327.

DOI: 10.1007/s00210-025-04421-3

[5] LUTZ T A. Mammalian ụdị ọrịa shuga mellitus, na-elekwasị anya na ụdị 2 ọrịa shuga mellitus[J]. Nyocha gbasara okike Endocrinology, 2023,19(6):350-360.

DOI: 10.1038/s41574-023-00818-3

[6] TU Q, LIU G, LIU X, et al. Echiche maka iji primates na-abụghị mmadụ na nyocha Exposome[J]. Ecotoxicology na nchekwa gburugburu, 2024,286:117199. DOI:10.1016/j.ecoenv.2024.117199.

Ngwaahịa niile, edemede, ngwa nka, nkọwa ngwaahịa, na ozi ndị ọzọ enyere na webụsaịtị a bụ naanị maka nyocha ụlọ nyocha ziri ezi, ozi, na ebumnuche nkuzi. 

Ngwaahịa ndị Cocer Peptides na-enye bụ naanị maka nyocha in vitro na ụlọ nyocha, echekwaghị ya maka iji mmadụ ma ọ bụ ọgwụgwọ anụmanụ, oriri mmadụ, ojiji ụlọ ọgwụ, iji nyocha, ọgwụgwọ ọgwụgwọ, ịgbakọta, nchịkwa onwe onye, ​​ịgba ọgwụ mgbochi ma ọ bụ ụdị ọ bụla ọzọ nke nchịkwa mmadụ ma ọ bụ anụmanụ. Ebughị n'obi ngwaahịa ndị a iji chọpụta, gwọọ, gwọọ, belata, ma ọ bụ gbochie ọrịa ọ bụla ma ọ bụ ọnọdụ ahụike, ma ọ bụ na ha ebughị n'obi metụta nhazi ma ọ bụ ọrụ nke ahụ mmadụ ma ọ bụ anụmanụ. Ọ gwụla ma ekwuputara nke ọma, ngwaahịa ndị enyere na webụsaịtị a enyochabeghị ma ọ bụ kwado ya site na nchịkwa nri na ọgwụ US (FDA) maka ojiji mmadụ ma ọ bụ ọgwụgwọ anụmanụ. Enyere ntụaka ọ bụla gbasara ọmụmụ akwụkwọ ebipụtara, ụzọ biochemical, usoro mkpụrụ ndụ, ma ọ bụ nchoputa nnwale naanị maka mkparịta ụka sayensị na ebumnuche nyocha na emeghị ndụmọdụ ahụike, nkwuputa ọgwụgwọ, ntuziaka dose, ma ọ bụ ntuziaka maka ojiji. Ndị na-azụ ahịa bụ naanị ọrụ ịhụ na enwetara, hazie, chekwaa, jiri ma tụfuo ya dịka iwu, ụkpụrụ, ihe ụlọ ọrụ chọrọ na ụkpụrụ nchekwa ụlọ nyocha siri dị.