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▎ Kūlana GLP-3
Puna: PubChem |
Kaʻina: YA⊃1;QGTFTSDYSI-L⊃2;LDKK⁴AQA⊃1;AFIEYLLEGGPSSGAPPPS⊃3; Hui Molekala: C 221H 342N 46O68 Kaumaha Molekala: 4731 g/mol Helu CAS: 2381089-83-2 PubChem CID: 171390338 Nā huaʻōlelo like:LY3437943 |
▎ ʻImi GLP-3
He aha ke kumu noiʻi o GLP-3?
ʻO ka momona kekahi o nā pilikia olakino o ka lehulehu i kēia mau lā. Hiki i ka momona ke alakaʻi i nā pilikia olakino like ʻole, e like me ke ʻano 2 metabolism, nā maʻi cardiovascular, hypertension, dyslipidemia, a me ka maʻi momona momona ʻole. Me ka hoʻomau mau ʻana o ka nui o ka momona, ke ulu nei ka noi no nā lāʻau lapaʻau hou e hiki ke mālama pono i ke kaumaha o ke kino a hoʻomaikaʻi i ke kūlana olakino [1] . ʻOiai ʻo ka hoʻololi ʻana i ke ʻano o ka nohona, e like me ka hoʻonui ʻana i ka hoʻoikaika kino a me ka hōʻemi ʻana i ka ʻai ʻana i ka meaʻai, ʻo ia nā ʻano kumu mua no ka mālama ʻana i ke kaumaha, ʻo ka mālama lōʻihi o ka pohō kaumaha he mea paʻakikī ia no nā poʻe mākua i hoʻopilikia ʻia. ʻO GLP-3 kahi agonist triple receptor hou e hana ana ma ka glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), a me ka glucagon receptor (GCGR). Hāʻawi kēia ʻano hana multi-receptor i nā pono kūʻokoʻa i ka pohō kaumaha. Ke hoʻohālikelike ʻia me nā lāʻau hoʻemi kaumaha e hana ana ma ka loaʻa hoʻokahi, hiki i ka GLP-3 ke hoʻoponopono piha i nā kaʻina metabolic o ke kino [1] . Loaʻa ka GLP-3 i ka pohō kaumaha ma o ka hoʻoponopono ʻana i nā mea loaʻa hormone. ʻAʻole wale ia he hopena koʻikoʻi koʻikoʻi akā loaʻa pū kekahi i nā hopena ʻaoʻao gastrointestinal maʻalahi. Eia kekahi, i ka hoʻohālikelike ʻia me nā lāʻau hōʻemi kaumaha hou, ʻo GLP-3, ma ke ʻano he triple receptor agonist, ʻoi aku ka ikaika o ka hopena kaumaha a me kahi ākea o nā heluna pili.
He aha ke ʻano o ka hana a GLP-3?
ʻO ke ʻano o ka hana a GLP-3 ka mea nui mai kona hopena agonistic i nā mea loaʻa he nui. ʻO ka mea mua, ʻo kona hopena agonistic ma ka glucagon-like peptide-1 receptor (GLP-1R) e hoʻonui i ka huna ʻana o ka insulin, e kāohi i ka huna ʻana o ka glucagon, e hoʻemi i ke kiʻekiʻe o ka glucose koko, a ma ka manawa like e hoʻopaneʻe i ka hoʻokaʻawale ʻana o ka ʻōpū, hoʻonui i ka satiety, a hoʻemi i ka ʻai ʻai [2] . ʻO ka lua, ʻo kona hopena agonistic i ka glucose-dependent insulinotropic polypeptide receptor (GIPR) hiki ke hoʻoikaika i ka huna ʻana o ka insulin, hoʻonui i ka hoʻohana ʻana i ka glucose, a loaʻa i ka hopena i ka momona metabolism, kaohi ʻana i ka lipolysis a me ka hoʻoikaika ʻana i ka synthesis momona [2] . Eia kekahi, ʻoiai ʻo ka hopena agonistic o GLP-3 ma ka glucagon receptor (GCGR) e hoʻolaha pinepine i ka glycogenolysis a me ka gluconeogenesis i loko o ke ake, e hoʻonui ana i nā pae glucose koko, ma lalo o ka hana a GLP-3, ua hoʻopau ʻia kēia hopena o ka hoʻonui ʻana i ke koko e nā hopena o nā mea ʻelua ʻē aʻe. I ka manawa like, hoʻoikaika ia i ka lipolysis a hoʻemi i ka hōʻiliʻili momona [2] . ʻOi aku ka maikaʻi o kēia ʻano hana multi-target i ka mālama ʻana i ka momona ma mua o nā agonists loaʻa hoʻokahi.
Ma ka hoʻoikaika like ʻana i kēia mau mea loaʻa ʻekolu, hiki i ka GLP-3 ke hana i nā ʻano hopena hoʻoponopono metabolic a hana i nā hopena therapeutic i ka momona a me nā maʻi pili. Ma ke ʻano o ka hoʻoponopono ʻana i nā pae glucose koko, ma muli o ka hoʻāla ʻana o GLP-1R a me GIPR e hāpai ana i ka huna ʻana o ka insulin a me ka pale ʻana i ka huna ʻana o ka glucagon, a me ka hoʻāla ʻana o GCGR i hoʻopau ʻia e nā hopena o nā mea ʻelua ʻē aʻe, hiki i ka GLP-3 ke hoʻoponopono maikaʻi i nā pae glucose koko, he mea nui ia no ka mālama ʻana i ke ʻano 2 metabolism [1,2] . Ma ke ʻano o ka hōʻemi ʻana i ka momona, hoʻoikaika ka GCGR i ka lipolysis a hōʻemi i ka hōʻiliʻili momona. I ka manawa like, hoʻonui ka hoʻoulu ʻana o GLP-1R i ka satiety a hoʻemi i ka ʻai ʻana i ka meaʻai, hoʻemi hou i ka synthesis momona [1, 2] . Eia kekahi, he hopena maikaʻi ko GLP-3 i ka maʻi ʻaʻai momona ʻole. Hiki iā ia ke hoʻemi i ka momona o ke ake a hoʻomaikaʻi i ka hana o ke ake. A randomized, double-blind, placebo-controlled trial i hōʻike ʻia ʻo ka awelika pili o ka hoʻololi ʻana i ka momona o ke akepaʻa i loko o ka hui mālama GLP-3 i nā wiki he 24 he haʻahaʻa haʻahaʻa ma mua o kēlā ma ka hui placebo [3].
HbA1c, ke kaumaha o ke kino, ke koko, a me ka lipid He mau huinaha li'ili'i loa ka 'ikepili (me nā pahu kuhi e hō'ike ana i nā SE) mai ka ho'onohonoho 'ana i ka pono, ke 'ole ka 'ike 'ana.
Puna:PubMed [4]
Pehea ʻo GLP-3 e hoʻoponopono ai i ka metabolism glucose ma hope o ka hoʻāla ʻana i nā mea loaʻa ʻekolu?
Hoʻoponopono ʻo GLP-3 i ka glucose koko ma o nā mīkini he nui, me ka hoʻoulu ʻana i ka GLP-1 a me GIP receptors, hoʻoulu i ka huna ʻana o ka insulin, kaohi ʻana i ka huna ʻana o ka glucagon, hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū, hoʻoponopono i ka metabolism momona, a hoʻemi i nā pae ANGPTL3/8. Ma ke ʻano o ka hoʻoponopono glucose koko, hana ʻo GLP-3 i nā mea loaʻa GLP-1 a me GIP, e hoʻoikaika ana i ka naʻau o nā cell pancreatic β i ka glucose, synthesizing a hoʻokuʻu i ka insulin, a laila hoʻoikaika i ka lawe ʻana a me ka hoʻohana ʻana i ka glucose e nā ʻiʻo, e loaʻa ana ka hopena o ka hōʻemi ʻana i ke koko glucose [4, 5] . (HbA1c), ka mea i pōmaikaʻi nui mai kāna hana i ka hoʻoulu ʻana i ka huna ʻana o ka insulin (Rosenstock J, 2023). I ka manawa like, hiki i ka hoʻoulu ʻana i ka mea loaʻa GLP-1 ke kāohi i ka huna ʻana o ka glucagon e nā pancreatic α cell, e pale ana i ke kiʻekiʻe o ka glucose koko. I loko o nā haʻawina hauʻoli, ua ʻike ʻia ua emi ka pae glucagon o nā maʻi e hoʻohana ana i ka GLP-3, ʻo ia hoʻi e kōkua i ka mālama ʻana i ka paʻa o ka glucose koko [4, 5] . ʻO ka hoʻoulu ʻana i nā mea loaʻa GLP-1 a me GIP hiki ke hoʻopaneʻe i ka nui o ka hoʻokuʻu ʻana o ka ʻōpū, hoʻolohi i ka hoʻoheheʻe ʻana a me ka ʻai ʻana o ka meaʻai, a hoʻemi i ka piʻi nui o ka glucose koko postprandial. Ua hōʻike ʻia nā haʻawina e hoʻolōʻihi nui ʻia ka manawa hoʻokaʻawale ʻana o ka ʻōpū o nā mea maʻi i mālama ʻia me GLP-3 ma hope o ka ʻai ʻana, no laila e hōʻemi ana i ka waiwai kiʻekiʻe o ka glucose koko postprandial [4].
ʻO ka hoʻoponopono ʻana i ka momona momona e GLP-3 e pili ʻole i ka metabolism glucose. No ka laʻana, ma nā noiʻi ʻana i nā maʻi obese, ua ʻike ʻia e hiki i ka GLP-3 ke hoʻemi i nā pae o ka triglycerides (TG), lipoprotein haʻahaʻa haʻahaʻa (LDL), a me ka lipoprotein haʻahaʻa haʻahaʻa loa (VLDL) cholesterol [2, 6] . ʻO kēia hoʻomaikaʻi ʻana i ka lipid metabolism e pili ana i ka hoʻomaikaʻi ʻana i ka naʻau o ka insulin, a laila e hāʻawi i ka hoʻokele glucose koko. Ma hope o ka hoʻomaʻamaʻa GLP-3, piʻi ka plasma 3-hydroxybutyric acid (3-HB), me ka piʻi ʻana o ka 3-hydroxybutyrylcarnitine (C 4OH), ka ratio o ka acetylcarnitine i ka carnitine manuahi (C 2/ C 0), a me ka medium-chain acylcarnitine, e hōʻike ana i ka lipolysis i hoʻonui ʻia i ka lipolysis.
Hiki i ka GLP-3 ke hoʻemi i ka huina dihydroceramides (DhCers), a pili kēia hoʻololi me ka hoʻomaikaʻi ʻana i ka insulin sensitivity, hōʻemi ʻia ka steatosis hepatic, a me ka mumū ʻōnaehana [6] . Ma ka manawa like, hiki i ka GLP-3 ke hoʻemi i ka ʻike o ka complex ANGPTL3 / 8 i loko o ka serum o nā maʻi metabolism type 2, hoʻoponopono i ka metabolism glucose [7] . ʻO ANGPTL3/8 ka mea hoʻopaneʻe kaʻapuni maikaʻi loa o ka lipoprotein lipase (LPL), a pili pono kona pae serum i ka TG a me ka lipoprotein cholesterol haʻahaʻa (LDL-C). Hoʻemi ʻo GLP-3 i ke kiʻekiʻe o ANGPTL3/8, hiki ke hoʻoponopono i ka metabolism glucose ma o ka hōʻemi ʻana i nā lipoproteins waiwai triglyceride [7] .
Ma nā ʻaoʻao hea e hōʻike ai ʻo GLP-3 i kona hopena?
Ka hopena o ke kaumaha nui:
Ua hōʻike ʻo GLP-3 i nā hopena paona koʻikoʻi i nā hoʻokolohua lapaʻau he nui. No ka laʻana, i loko o kahi noiʻi lapaʻau e pili ana i 338 mau mākua [2] , ua loaʻa i nā poʻe maʻi i mālama ʻia me nā kumu like ʻole o GLP-3 i ka pohō kaumaha nui ma 48 pule. Ma waena o lākou, ua loaʻa i ka poʻe maʻi i ka hui 12mg dose ka pohō kaumaha o 24.2%, a he hapa nui o nā mea maʻi i loaʻa i ka pohō kaumaha i nā pae like ʻole. No ka laʻana, ma waena o nā poʻe maʻi e loaʻa ana i ka 4mg, 8mg, a me 12mg doses, 92%, 100%, a me 100% o nā maʻi i nalowale i ka 5% a i ʻole ke kaumaha o ko lākou kino. Ma kekahi noiʻi ʻē aʻe [8] , ua hōʻike ʻia ʻelua mau hoʻokolohua i hoʻopaʻa ʻia e pili ana i nā mea maʻi metabolism 353 type 2 i ka hoʻohālikelike ʻia me ka placebo, hiki i ka GLP-3 ke hoʻemi nui i ke kaumaha o ke kino o nā maʻi e 11.89kg a hoʻemi i ka hemoglobin glycated (HbA1C). Eia kekahi, i ka hoʻāʻo ʻana o nā poʻe maʻi ʻaʻohe maʻi maʻi obese, ua hoʻolilo ʻo GLP-3 i ke kaumaha o 24.2% i nā mea maʻi, a ʻo 83% o nā maʻi i nalowale he 15% a i ʻole ke kaumaha o ko lākou kino ma 48 mau pule. Hōʻike kēia mau hualoaʻa he mana nui ko GLP-3 i ka pohō kaumaha.
Hoʻomaʻamaʻa i ka metabolism type 2 :
Hōʻike pū ʻia ʻo GLP-3 i kekahi mau mea hiki i ka mālama ʻana i ke ʻano 2 metabolism. I kekahi mau hoʻokolohua lapaʻau, ua hōʻike ʻo GLP-3 i ka emi ʻana o ka hemoglobin glycated (HbA1c) a me ka pohō kaumaha. No ka laʻana, i loko o kahi noiʻi, i nā maʻi metabolism type 2, ua hōʻike ʻo GLP-3 i kahi hopena koʻikoʻi o ka hoʻokele glucose koko, e hōʻemi ana i ka hemoglobin glycated e 1.64% i hoʻohālikelike ʻia me ka placebo [4, 8] . Eia hou, i ka randomized, double-blind, placebo, and active-controlled parallel-group phase 2 ho'āʻo, holoholona kŘkohu me ka type 2 metabolism i hōʻike nui i ka glycated hemoglobin pae a me ka dose-pili kaumaha poho ma hope o ka loaʻaʻana o GLP-3 lapaʻau [4] . Hiki ke hoʻopili ʻia kēia i nā hopena piha o ka lāʻau lapaʻau ma GLP-1, GCGR, a me GIPR, e hoʻomaikaʻi ai i ka metabolism glucose a me ke koena o ka ikehu.
Ka hoʻomaikaʻi ʻana i nā kumu pilikia cardiovascular:
ʻAʻole hiki i ka GLP-3 ke hōʻemi wale i ke kaumaha o ke kino akā hoʻomaikaʻi pū kekahi i nā mea pilikia cardiovascular, e like me ka serum lipid profile a me nā pae hemoglobin glycated. Hōʻike kēia i kahi pilina pili pathophysiological ma waena o ka momona a me nā maʻi cardiovascular, a hiki i ka GLP-3 ke hoʻomaikaʻi i ke olakino cardiovascular o nā maʻi obese ma o nā ala he nui. Eia kekahi laʻana, hiki i ka ho'ēmiʻana i nā pae non-HDL-C, apoB, a me LDLP ke hoʻemi i ka pilikia o ke atherosclerosis; ʻO ka hoʻohaʻahaʻa ʻana i nā pae hemoglobin glycated hiki ke hoʻomaikaʻi i ka mana glucose koko i nā mea maʻi metabolism, a laila e hōʻemi ana i ka hopena o nā pilikia cardiovascular [8-10] .
Lapaʻau ʻana i ka maʻi ʻaʻai momona ʻole (NAFLD):
ʻO GLP-3 kahi puke hou triple receptor agonist peptide e kuhikuhi ana i ka glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), a me ka glucagon-like peptide-1 receptor (GLP-1R). Ua hōʻike ʻia nā haʻawina e hiki i ka GLP-3 ke mālama i ka maʻi ʻaʻai momona ʻole. I loko o kahi noiʻi, ua mālama ʻia kahi hoʻokolohua randomized, pālua-makapō, placebo-controlled hoʻāʻo ʻo 48 mau pule ma luna o nā poʻe me nā maʻi momona momona pili i ka metabolic dysfunction a me kahi momona momona o ≥10%. Ua hōʻike ʻia nā hopena i nā wiki he 24, ʻo ka awelika o ka hoʻololi ʻana i ka momona o ke akepaʻa e pili ana i ka baseline i nā poʻe hui i mālama ʻia me nā ʻokoʻa like ʻole o GLP-3 (1mg, 4mg, 8mg, a me 12mg) he -42.9%, -57.0%, -81.4%, a me -82.4%, i kēlā me kēia, ʻoiai ʻo ia ma ka hui placebo he +0.3 % . Hōʻike kēia e loaʻa paha i ka GLP-3 kahi hopena therapeutic koʻikoʻi i ka maʻi momona momona ʻole.
I ka hopena, ma ke ʻano he triple receptor agonist, hōʻike ʻo GLP-3 i ka mana nui i ka mālama ʻana i ka momona a me nā maʻi pili. Hiki iā ia ke hoʻoikaika i ka mea hoʻokipa glucagon, ka mea hoʻokipa insulinotropic polypeptide e pili ana i ka glucose, a me ka glucagon-like peptide-1 receptor, hoʻoponopono piha i ka metabolism o ke kino mai nā ʻāpana he nui, hoʻomaikaʻi i ka mana glucose koko, hōʻemi i ke kaumaha o ke kino, a hoʻoponopono i ka metabolism lipid. ʻO ka puka ʻana o GLP-3 e lawe mai i nā koho lapaʻau hou no nā poʻe maʻi me ka momona, type 2 metabolism, a me nā maʻi ʻē aʻe. Manaʻo ʻia e uhaki i nā palena o nā lāʻau agonist agonist kuʻuna hoʻokahi, e hāʻawi i kahi mea kaua ikaika loa no ka hoʻoponopono ʻana i nā pilikia koʻikoʻi o ka momona a me nā maʻi metabolic, e hoʻoikaika i ka hoʻomohala hou ʻana o nā lāʻau lapaʻau pili, hoʻomaikaʻi i ka maikaʻi o ke ola o nā maʻi, a hoʻemi i ke kaumaha olakino.
No ka mea kakau
ʻO nā mea i ʻōlelo ʻia ma luna nei ua noiʻi ʻia, hoʻoponopono ʻia a hōʻuluʻulu ʻia e Cocer Peptides.
Mea kākau moʻolelo ʻepekema
He loea koʻikoʻi ʻo Rosenstock J i ka ʻoihana lapaʻau, e pili pū ana me nā hui e like me ke Kulanui o Texas Southwestern Medical Center a me ke Kulanui o Texas Dallas. Ke alakaʻi nei ʻo ia i ka noiʻi ma nā kikowaena e like me ka Canadian VIGOR Center a me Veloc Clin Res Ctr Med City. ʻO kāna noiʻi e pili ana i ka endocrinology a me ka metabolism, ka ʻōnaehana cardiovascular a me ka cardiology, pharmacology, a me ka lāʻau hoʻokolohua, me ka nānā ʻana i ka metabolism, ka momona, a me nā lāʻau pili a me ka hoʻomohala ʻana i ka lāʻau. Ua loaʻa iā J Rosenstock ka lanakila nui ma ka lāʻau lapaʻau, ua kapa ʻia ʻo Highly Cited Researcher mai 2017 a 2024. Hōʻike kēia i ka hopena kiʻekiʻe a me ka ʻike ākea o kāna hana. Ma o ka launa pū ʻana me nā keʻena noiʻi lehulehu, ua unuhi maikaʻi ʻo ia i nā ʻike noiʻi kumu i loko o nā noi lapaʻau, e pōmaikaʻi ana i nā poʻe maʻi me nā maʻi metabolic a me ka maʻi cardiovascular a me ka holomua ʻana i ka ʻepekema lapaʻau. Ua helu ʻia ʻo Rosenstock J ma ka ʻōlelo kuhikuhi [4].
