Retatrutid (GLP-3) ƒe atike si nye 10mg

▎ GLP-3 ƒe Dɔwɔɖoɖo

▎ Molekyulãwo ƒe Nɔnɔme

GLP-3 (LY3437943) nye numekuku peptide si woɖɔ be enye etɔ̃ xɔla agonist le glucagon-like peptide-1 xɔla (GLP-1R), sukli-dzikpɔkpɔ insulinotropic polypeptide xɔla (GIPR), kple glucagon xɔla (GCGR).[1,2]

Fig1. Dɔlékuixɔla ƒe mɔ etɔ̃ siwo ŋu woƒo nu tsoe na GLP-3 le numetoto si woyɔ me ƒe nɔnɔmetata si wowɔ ɖe ɖoɖo nu.[1]

Numekuku ƒe Ŋgɔyiyi

Coskun, Tamer, kple eƒe dɔwɔhatiwo srɔ̃ nu tso GLP-3 ŋu le C57/Bl6 nuɖuɖu si lolo akpa (DIO) mice me. Agbalẽa ŋlɔlawo ka nya ta be tɔtrɔ siwo nɔa te ɖe agbɔsɔsɔme si wozãna dzi le ame ƒe kpekpeme, nuɖuɖumeŋusẽ si woxɔna, ŋutilã ƒe wɔwɔme, sukli si le ʋu me, insulin, ALT, kple aklã me triglycerides me. Wozã dodokpɔ bubu siwo wowɔ le numekuku ma ke me tsɔ lé ŋku ɖe akpa si GCGR, GIPR, kple GLP-1R ƒe dzesiwo wɔna le ŋuɖoɖo siwo wokpɔ do ŋgɔ na dɔdamɔnua me ŋu.[2]

Fig2. Woka nya ta tso ŋutilã ƒe kpekpeme, nuɖuɖumeŋusẽ si woxɔna, ŋutilã ƒe wɔwɔme, kple lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe nuwuwu ŋu na LY3437943 le mice lolo akpa siwo nuɖuɖu hena vɛ me.[2]

Woxɔ LY3437943 ƒe agbɔsɔsɔ si dzina ɖe edzi zi ɖeka gbesiagbe (QD) si lolo akpa siwo nuɖuɖu na hena ŋkeke 21 le numekuku si woyɔ me.

(A) Tɔtrɔ le ame ƒe kpekpeme le alafa me le ɣeyiɣi aɖe megbe.

(B) Calorie si woɖuna ƒe ƒuƒoƒo le ɣeyiɣi aɖe megbe.

(C – F) Ŋutilã ƒe wɔwɔme ƒe tɔtrɔ le gram me le numekukua ƒe nuwuwu: ŋutilã ƒe kpekpeme (C), ami ƒe agbɔsɔsɔ (D), ami ƒe agbɔsɔsɔ (E), kple ami ƒe lolome/ami ƒe xexlẽme ƒe sɔsɔme (F).

(G – J) Lãmetsiŋusẽ ƒe nɔnɔmewo le numekukua ƒe nuwuwu: ʋumesukli (G), insulin (H), ALT (I), kple aklã me triglycerides (J).

(K) LY3437943 tsɔtsɔ sɔ kple GLP-2 le agbɔsɔsɔme si numekukua gblɔ me hena tɔtrɔ le alafa me le ŋutilã ƒe kpekpeme me le ɣeyiɣi aɖe megbe.

(L) LY3437943 tsɔtsɔ sɔ kple GLP-2 le agbɔsɔsɔ si numekukua gblɔ me hena calorie ɖuɖu le ɣeyiɣi aɖe megbe.

Woɖea nyatakakawo fiana abe mama dedie ± SEM ene kple n = 6 (A – L). akɔntabubu me dzodzro le (C) – (K) me to mɔ ɖeka dzi ANOVA tsɔtsɔ sɔ kple ʋu zazã me, eye woɖe vevienyenye gɔme le p < 0.05. Wowɔ ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001 ne wotsɔe sɔ kple ʋu, p < 0.05 ne wotsɔe sɔ kple GLP-2. ALT, si nye alanine aminotransferase, si nye atike si woyɔna be alanine aminotransferase; LY, LY3437943, kple LY3437943; SEM, vodada si woɖo ɖi le mama dedie nu.+

Li, Wenzhuo, kple ame bubuwo. zã cryo-electron microscopy tsɔ do GLP-3 si bla ɖe GLP-1R, GIPR, kple GCGR ŋu kpɔ. Agbalẽa ŋlɔlawo ka nya ta be peptide la ƒe N-nuwuƒe ƒe akpaa wɔa dɔ kple kotoku si blaa nulénu si le lãkusia me, evɔ C-nuwuƒe ƒe nuto ya kpena ɖe kadodo kple lãmenugbagbevi siwo le lãmenugbagbeviwo godo ƒe nuto siwo me woxɔa nu le ŋu. Numekukua de dzesi kadodo siwo wodzra ɖo kple esiwo ku ɖe xɔla tɔxɛwo ŋu siaa le xɔla ƒe ƒuƒoƒo etɔ̃awo me.[3]

Joachim Neumann kple eƒe dɔwɔhatiwo do GLP-3 kpɔ le amegbetɔ ƒe ɖusime dzitodzito ƒe dzadzraɖo siwo woɖe ɖe aga siwo woxɔ le dzidɔdada me. Agbalẽa ŋlɔlawo ka nya ta tso tɔtrɔ siwo nɔa te ɖe susu ƒe dɔwɔwɔ kple ɣeyiɣi dzi le ŋusẽ si wotsɔna ƒoa ʋu ƒe sisi me eye wozã atike siwo xea mɔ na dɔlélea tsɔ ku nu me le GCGR, GIPR, kple GLP-1R ƒe gomekpɔkpɔ le eme ŋu. Wodo dzesi ƒe mɔnu si do ƒome kple cAMP ɖe ŋgɔ le ex vivo numekuku sia ƒe nɔnɔmewo me.[4]

Coskun kple exɔlɔ̃wo. hã ka nya ta tso dzitodzito ƒe dedienɔnɔ ŋuti numekuku siwo menye dɔdamɔnu o ŋuti numekuku siwo wowɔ le boso siwo nye cynomolgus ŋu. Le numekuku si wowɔ le agbɔsɔsɔ ɖeka me me la, dzi ƒe tsotso sɔ gbɔ wu amesiwo ŋu wokpɔ ŋusẽ ɖo le ɣeyiɣi ɖeka me le LY3437943 zazã vɔ megbe, eye numekukua ƒe agbɔsɔsɔme si lolo wue na dzidziɖedzi gãtɔ. Le ɣleti ade ƒe numekuku si wowɔ le atikeawo zazã ake me la, wokpɔ dzi ƒe tsotso si nu sẽ wu le atikeawo zazã ƒe akpaa me eye wogblɔ be enɔ te ɖe agbɔsɔsɔme si wozã dzi; woka nya ta tso tɔtrɔ siwo va le ʋu ƒe sisi le ʋuka me kple ʋu ƒe sisi le ʋuka me hã ŋu.[2] Wowɔ ŋkuléleɖenuŋu siawo le nɔnɔme siwo me womewɔ numekuku le le primate siwo menye amegbetɔwo o me.

Numekuku ƒe Seɖoƒewo

Lãwo ƒe kpɔɖeŋuwo naa nyatakakawo le dodokpɔ ƒe nɔnɔme siwo woɖe fia me gake womate ŋu agbugbɔ amegbetɔ ƒe ŋutilã ƒe dɔwɔwɔ ƒe sesẽme awɔ bliboe o. Vovototo si le receptor biology, neuroendocrine ƒe tɔtrɔ ɖe nɔnɔmewo ŋu, ɣeyiɣi didi si woatsɔ akpɔe, kple dzesi siwo le anyime ate ŋu akpɔ ŋusẽ ɖe gbegɔmeɖeɖe dzi le lã ƒomevi vovovowo me. Eyata ele be woaɖe nusiwo wokpɔ tso dɔlélenutsiŋutete ƒe dodokpɔwo, xɔtuɖaŋu ŋuti numekukuwo, amegbetɔ ƒe lãkusi siwo woɖe ɖe aga, kple lãwo ƒe kpɔɖeŋuwo me gɔme le kpɔɖeŋu si wozã me eye mele be woabu wo be wonye kpeɖodzi be dɔdaƒe ƒe dedienɔnɔ alo dɔwɔwɔ nyuie o.[2,4-6]

COCER Peptides naa GLP-3 hena numekuku zazã le nudokpɔƒe ɖeɖeko ke menye na amegbetɔwo alo lãwo ƒe zazã o. Nyatakaka siwo le axa sia gblɔ nusiwo ŋu woke ɖo siwo ŋu woka nya ta le le ame bubuwo ƒe agbalẽ siwo woyɔ me kpuie eye womegblɔ nya aɖeke ku ɖe dɔdamɔnu ƒe dɔwɔwɔ, dedienɔnɔ, dɔlélewo didi, atikewɔwɔ, mɔxexe ɖe enu, alo amegbetɔwo ƒe zazã bubuwo ŋu o.

▎ Nyayɔyɔ Siwo Sɔ

[1] KAUR M, MISRA S. Numekuku ƒe atike GLP-3, si nye atike yeye si nye agonist etɔ̃ ƒe atike si wotsɔ daa lolo akpa ƒe numetoto[J]. Europa ƒe Atikeŋutinunya ƒe Agbalẽ, 2024,80 (5): 669-676.

DOI: 10.1007/s00228-024-03646-0

[2] COSKUN T, URVA S, ROELL WC, kple ame bubuwo. LY3437943, si nye glucagon etɔ̃, GIP, kple GLP-1 receptor agonist yeye aɖe hena suklidɔ dzi ɖuɖu kple lolo dzi ɖeɖe kpɔtɔ: Tso nusi ŋu woke ɖo dzi va ɖo susua ƒe kpeɖodzi le dɔdaƒe dzi[J]. Lãmenugbagbeviwo ƒe Suklidɔ, 2022, 34 (9): 1234-1247.e9.

DOI: 10.1016/j.cmet.2022.07.013 ƒe agbalẽa me

[3] LI W, ZHOU Q, CONG Z, kple ame bubuwo. Dɔwɔɖoɖo ŋuti gɔmesesewo le agonistism etɔ̃ ŋu le GLP-1R, GIPR kple GCGR si GLP-3[J] ɖe fia. Lãmenugbagbeviwo ƒe Kekeɖenudɔwɔwɔ, 2024,10:77.

DOI: 10.1038/s41421-024-00700-0

[4] NEUMANN J, AHLREP U, HOFMANN B, kple ame bubuwo. GLP-3 ƒe inotropic ŋusẽkpɔɖeamedziwo le amegbetɔ ƒe dzitodzito me dzadzraɖo siwo woɖe ɖe aga me[J]. Naunyn-Schmiedeberg ƒe Atikeŋutinunya ƒe Nudzraɖoƒe, 2026,399 (1): 317-327.

DOI: 10.1007/s00210-025-04421-3

[5] LUTZ T A. No me lãwo ƒe suklidɔ ƒe kpɔɖeŋuwo, kple susu ɖe suklidɔ ƒomevi 2 ŋu[J]. Dzɔdzɔme Totoɖeme Endocrinology, 2023,19 (6): 350-360.

DOI: 10.1038/s41574-023-00818-3

[6] TU Q, LIU G, LIU X, kple ame bubuwo. Nukpɔsusu le primate siwo menye amegbetɔwo o zazã ŋu le Exposome numekuku me[J]. Nutoa me ƒe aɖiŋutinunya kple Nutome ƒe Dedienɔnɔ, 2024,286:117199. DOI:10.1016/j.ecoenv.2024.117199.

WOÐO NUSIWO KAtã, NYATAKAKAWO, Mɔ̃ɖaŋununyaWO, AKPAÐEKAWO ƑE NUMEÐEÐEWO, KPLEE NYATAKAKA BUBU SIWO WOÐO LE NYATAKAKADZRAÐOƑE SIA ME NA NUMEKUKU, NYATAKAKAWO, KPLEE HEHENANA ƑE TAÐOÐO SIWO LE SE KO. 

Wotrɔ asi le atike siwo Cocer Peptides naa ŋu na numekuku le vitro kple nudokpɔƒe ɖeɖeko eye MENYE ɖe wowɔe na amegbetɔwo alo lãwo ƒe zazã, amegbetɔwo ƒe nuɖuɖu, atikewɔƒewo zazã, dɔlélewo didi ƒe zazã, atikewɔwɔ, atikewo tsɔtsɔ kpe ɖe wo nɔewo ŋu, wo ɖokui dodo na wo ɖokui, wo dodo ɖe lãme na ame, alo wo dodo na amegbetɔwo alo lãwo ƒe mɔnu bubu aɖeke o. Menye ɖe wowɔ atike siawo be woatsɔ ade dzesi dɔléle alo atikewɔwɔ ƒe nɔnɔme aɖeke, adae, adae, aɖe edzi akpɔtɔ, alo axe mɔ ɖe enu o, eye womeɖoe be woakpɔ ŋusẽ ɖe amegbetɔ alo lãwo ƒe ŋutilã ƒe wɔwɔme alo dɔwɔwɔ dzi hã o. Negbe ɖe wogblɔe tẽe ko hafi United States ƒe Nuɖuɖu Kple Atike Ŋuti Dɔwɔƒe (FDA) meda atike siwo wotsɔ na le nyatakakadzraɖoƒe sia kpɔ alo da asi ɖe wo dzi be woazã na amegbetɔwo alo lãwo o. Wotsɔ nya ɖesiaɖe si ku ɖe numekuku siwo wota, nugbagbeŋusẽ ƒe mɔnuwo, molecule ƒe dɔwɔwɔ, alo dodokpɔ me nusiwo ŋu woke ɖo ŋu na dzɔdzɔmeŋutinunya me numedzodzro kple numekuku ƒe taɖodzinuwo ko eye menye atikewɔwɔ ŋuti aɖaŋuɖoɖo, atikewɔwɔ ŋuti nyagbɔgblɔ, agbɔsɔsɔme si woazã ŋuti mɔfiame, alo mɔfiame siwo ku ɖe ezazã ŋu o. Nuƒlelawo ɖeɖeko ƒe agbanɔamedzie wònye be woakpɔ egbɔ be woxɔ nuawo katã, wokpɔ wo gbɔ, wodzra wo ɖo, zã wo, eye wotsɔ wo ƒu gbe le se, ɖoɖo, dɔwɔƒea ƒe nudidiwo, kple nudokpɔƒe ƒe dedienɔnɔ ƒe dzidzenu siwo li nu.