Retatrutid (GLP-3) 10mg

▎ Kūlana GLP-3

▎ Molekula Kahua

ʻO GLP-3 (LY3437943) kahi peptide noiʻi i wehewehe ʻia he triple receptor agonist ma ka glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), a me ka glucagon receptor (GCGR).[1,2]

Fig1. Hōʻike hoʻolālā o nā ala ʻekolu i kūkākūkā ʻia no GLP-3 ma ka loiloi i ʻōlelo ʻia.[1]

Holomua noiʻi

Ua aʻo ʻo Coskun, Tamer, a me nā hoa hana i ka GLP-3 i nā ʻiole C57/Bl6 diet-induced obesity (DIO). Ua hōʻike nā mea kākau i nā loli e pili ana i ka nui o ke kino, ka lawe ʻana i ka calorie, ka haku ʻana o ke kino, ka glucose koko, insulin, ALT, a me nā triglycerides ate. Ua hoʻohana ʻia nā hoʻokolohua ʻē aʻe ma ka haʻawina like e nānā i ka hāʻawi ʻana o GCGR, GIPR, a me GLP-1R hōʻailona i nā pane preclinical i ʻike ʻia.[2]

Fig2. ʻO ke kaumaha o ke kino, ka calorie-intake, ke kino-composition, a me metabolic endpoints i hōʻike ʻia no LY3437943 i nā ʻiole obese i hoʻokomo ʻia i ka ʻai.[2]

Loaʻa i nā ʻiole obese ʻai i hoʻokahi manawa i kēlā me kēia lā (QD) piʻi ʻia o LY3437943 no nā lā 21 i ka haʻawina i haʻi ʻia.

(A) Hoʻololi i ka pākēneka o ke kaumaha o ke kino i ka manawa.

(B) ʻO ka lawe ʻana i ka calorie kumulative i ka manawa.

(C – F) Hoʻololi ka hoʻohui kino ʻana i nā grama ma ka pau ʻana o ke aʻo ʻana: ke kaumaha o ke kino (C), ka momona momona (D), ka nui lean (E), a me ka ratio lean/fat mass (F).

(G – J) Nā ʻāpana olakino metabolic ma ka hopena o ke aʻo ʻana: ka glucose koko (G), insulin (H), ALT (I), a me nā triglycerides ate (J).

(K) Hoʻohālikelike o LY3437943 me GLP-2 ma ka haʻawina i hoʻopaʻa ʻia no ka pākēneka hoʻololi o ke kaumaha o ke kino i ka manawa.

(L) Hoʻohālikelike o LY3437943 me GLP-2 ma ke ʻano haʻawina i hoʻopaʻa ʻia no ka lawe ʻana i ka calorie i ka manawa.

Hōʻike ʻia ka ʻikepili ma ke ʻano he ± SEM me n = 6 (A – L). Ua hana ʻia ka ʻikepili helu ma (C) - (K) me ka hoʻohana ʻana i ka ANOVA ala hoʻokahi me ke kaʻa, me ka manaʻo nui i wehewehe ʻia ma p <0.05. ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p <0.001, ∗∗∗∗ p <0.0001 me ke kaʻa, p <0.05 me GLP-2. ALT, alanine aminotransferase; LY, LY3437943; SEM, hapa maʻamau o ka mean.+

Li, Wenzhuo, et al. ua hoʻohana i ka microscopy cryo-electron e nānā i ka GLP-3 i hoʻopaʻa ʻia i GLP-1R, GIPR, a me GCGR. Ua hōʻike nā mea kākau e pili ana ka ʻāpana N-terminal o ka peptide me ka ʻeke hoʻopaʻa transmembrane receptor, aʻo ka ʻāpana C-terminal e hāʻawi i nā pilina me nā ʻāpana ʻāpana extracellular. Ua ʻike ʻia ka haʻawina i nā mea pili i mālama ʻia a me nā mea hoʻopili kikoʻī ma waena o nā paʻakikī ʻekolu.[3]

Ua nānā ʻo Joachim Neumann a me nā hoa hana i ka GLP-3 i ka hoʻomākaukau ʻana i ka atrial pono kanaka i loaʻa i ka wā o ka ʻoki puʻuwai. Ua hōʻike nā mea kākau i ka hoʻololi ʻana i ka noʻonoʻo- a me ka manawa e hilinaʻi nei i ka ikaika o ka contraction a ua hoʻohana i nā antagonist receptor e noiʻi i ke komo ʻana o GCGR, GIPR, a me GLP-1R. Ua manaʻo lākou i kahi hana hōʻailona pili i ka cAMP ma lalo o nā kūlana o kēia haʻawina ex vivo.[4]

ʻO Coskun et al. ua hōʻike pū ʻia nā haʻawina palekana cardiovascular nonclinical i nā monkey cynomolgus. Ma kahi hoʻopaʻa haʻawina hoʻokahi, ʻoi aku ka kiʻekiʻe o ka puʻuwai ma mua o nā mana like ma hope o ka hoʻolaha ʻana o LY3437943, me ka nui o ka haʻawina haʻawina e hoʻonui ai. I loko o kahi noiʻi hou-dose ʻeono mahina, ua ʻike ʻia ka piʻi ʻana o ka puʻuwai kiʻekiʻe i ka wā o ka hoʻopaʻa ʻana a ua wehewehe ʻia ʻo ia e pili ana i ka dosis; Ua hōʻike pū ʻia nā loli i ke koko systolic a me ka diastolic.[2] Ua hana ʻia kēia mau ʻike ma lalo o nā kūlana haʻawina primate ʻaʻole kanaka.

Nā palena noiʻi

Hāʻawi nā ʻano holoholona i ka ʻike ma lalo o nā kūlana hoʻokolohua i wehewehe ʻia akā ʻaʻole hiki ke hoʻopuka piha i ka paʻakikī o ka physiology kanaka. Hiki ke hoʻololi i ka unuhi ʻana ma waena o nā ʻano mea ʻokoʻa ka ʻokoʻa o ka biology receptor, neuroendocrine adaptation, ka lōʻihi o ka hoʻolaha ʻana, a me ka hōʻailona o lalo. No laila, pono e unuhi ʻia nā ʻike mai nā mea hoʻokipa, nā haʻawina hoʻolālā, nā ʻiʻo kanaka i hoʻokaʻawale ʻia, a me nā ʻano holoholona i loko o ke kumu hoʻohālike i hoʻohana ʻia a ʻaʻole pono e mālama ʻia ma ke ʻano he hōʻike no ka palekana a i ʻole ka pono.[2,4-6]

Hāʻawi ʻo COCER Peptides i ka GLP-3 wale nō no ka hoʻohana ʻana i ka noiʻi hale hana a ʻaʻole no ka hoʻohana ʻana i ke kanaka a i ʻole nā ​​​​mea holoholona. ʻO ka mea ma kēia ʻaoʻao e hōʻuluʻulu i nā ʻike i hōʻike ʻia i loko o nā palapala a nā ʻaoʻao ʻekolu i ʻōlelo ʻia a ʻaʻole hoʻopiʻi e pili ana i ka pono lapaʻau, palekana, hōʻoia, mālama, pale ʻana, a i ʻole hoʻohana kanaka.

▎ Nā ʻōlelo pili

[1] KAUR M, MISRA S. He loiloi o kahi lāʻau noiʻi GLP-3, kahi mea hou triple agonist agent no ka mālama ʻana i ka momona [J]. European Journal of Clinical Pharmacology, 2024,80(5):669-676.

DOI:10.1007/s00228-024-03646-0

[2] COSKUN T, URVA S, ROELL WC, a me al. LY3437943, kahi moʻolelo triple glucagon, GIP, a me GLP-1 receptor agonist no ka mana glycemic a me ka poho kaumaha: Mai ka ʻike ʻana i ka hōʻoia hōʻoia o ka manaʻo [J]. Cell Diabetes, 2022,34(9):1234-1247.e9.

DOI:10.1016/j.cmet.2022.07.013

[3] LI W, ZHOU Q, CONG Z, a me al. Nā ʻike hoʻolālā i ka triple agonism ma GLP-1R, GIPR a me GCGR i hōʻike ʻia e GLP-3[J]. ʻIke Pūnaewele, 2024,10:77.

DOI:10.1038/s41421-024-00700-0

[4] NEUMANN J, AHLREP U, HOFMANN B, et al. Nā hopena inotropic o GLP-3 i ka hoʻomākaukau ʻana o ke kanaka atrial [J]. Naunyn-Schmiedeberg's Archives of Pharmacology, 2026,399 (1): 317-327.

DOI:10.1007/s00210-025-04421-3

[5] LUTZ T A. ʻO nā hiʻohiʻona maʻamau o ka maʻi diabetes mellitus, me ka nānā ʻana i ka maʻi diabetes type 2 [J]. Nānā Natura Endocrinology, 2023,19(6):350-360.

DOI:10.1038/s41574-023-00818-3

[6] TU Q, LIU G, LIU X, et al. Manaʻo ma ka hoʻohana ʻana i nā primates ʻaʻole kanaka ma ka noiʻi Exposome[J]. Ecotoxicology a me ka Maluhia Kaiapuni, 2024,286:117199. DOI:10.1016/j.ecoenv.2024.117199.

ʻO nā huahana a pau, nā ʻatikala, nā mea ʻenehana, nā wehewehe ʻana i nā huahana, a me nā ʻike ʻē aʻe i hāʻawi ʻia ma kēia pūnaewele, ua manaʻo wale ʻia no ka noiʻi LABORATORY pono, ka ʻike, a me nā kumu hoʻonaʻauao. 

ʻO nā huahana i hāʻawi ʻia e Cocer Peptides i manaʻo wale ʻia no ka noiʻi in vitro a me ka noiʻi ʻana a ʻaʻole i manaʻo ʻia no ka hoʻohana ʻana i ke kanaka a i ʻole nā ​​​​mea holoholona, ​​​​ka ʻai kanaka, ka hoʻohana lāʻau lapaʻau, ka hoʻohana diagnostic, ka hoʻohana therapeutic, ka hoʻohui ʻana, ka hoʻokele ponoʻī, ka injection, a i ʻole kekahi ʻano hoʻokele i ke kanaka a i ʻole nā ​​holoholona. ʻAʻole i manaʻo ʻia kēia mau huahana e hōʻoia, mālama, hoʻōla, hoʻēmi, a pale i kekahi maʻi a i ʻole maʻi olakino, ʻaʻole lākou i manaʻo e hoʻopilikia i ke ʻano a i ʻole ka hana o ke kino kanaka a holoholona. Inā ʻaʻole i haʻi pololei ʻia, ʻaʻole i loiloi ʻia nā huahana i hāʻawi ʻia ma kēia pūnaewele a ʻae ʻia e ka US Food and Drug Administration (FDA) no ka hoʻohana ʻana i ke kanaka a i ʻole ka holoholona. Hāʻawi ʻia nā kuhikuhi i nā noiʻi i paʻi ʻia, nā ala biochemical, nā mīkini molekala, a i ʻole nā ​​​​ʻike hoʻokolohua e hāʻawi wale ʻia no ke kūkākūkā ʻepekema a me nā kumu noiʻi a ʻaʻole ia he ʻōlelo aʻoaʻo lapaʻau, koi therapeutic, alakaʻi dosing, a ʻōlelo paha no ka hoʻohana. ʻO nā mea kūʻai wale nō ke kuleana no ka hōʻoia ʻana ua loaʻa nā huahana a pau, mālama ʻia, mālama ʻia, hoʻohana ʻia, a hoʻokuʻu ʻia e like me nā kānāwai pili, nā hoʻoponopono, nā koi ʻoihana, a me nā kūlana palekana lab.