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▎ ʻImi GLP-3
He aha ke kumu noiʻi o GLP-3?
Ua lilo ʻo Obesity i kekahi o nā pilikia olakino koʻikoʻi i ka nohona o kēia wā. Hiki iā ia ke hoʻoulu i nā pilikia olakino e like me ke ʻano 2 metabolism mellitus, nā maʻi cardiovascular, hypertension, dyslipidemia, a me ka maʻi momona momona ʻole. Me ka piʻi mau ʻana o ka nui o ka momona, aia ka makemake nui no nā lāʻau lapaʻau hou e hiki ke mālama pono i ke kaumaha o ke kino a hoʻomaikaʻi i nā kūlana olakino [1] . ʻOiai ʻo ka hana ʻana o ka nohona, e like me ka hoʻonui ʻana i ka hoʻoikaika kino a me ka mālama ʻana i ka meaʻai, ʻo ia ke kumu nui no ka mālama ʻana i ke kaumaha, he paʻakikī loa i nā poʻe maʻi obese makua ke mālama i ka pohō kaumaha no ka wā lōʻihi.
ʻO GLP-3, ma ke ʻano he triple receptor agonist hou, hiki ke hana i ka glucagon-like peptide-1 receptor (
ʻO GLP-1R), ka mea hoʻokipa insulinotropic polypeptide e pili ana i ka glucose (GIPR), a me ka mea hoʻokipa glucagon (GCGR). Hāʻawi kēia ʻano hana multi-receptor iā ia me nā pōmaikaʻi koʻikoʻi ma ke kahua o ka pohō kaumaha. Ke hoʻohālikelike ʻia me nā lāʻau hoʻemi kaumaha e hana ana ma ka loaʻa hoʻokahi wale nō, 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 he nui, ʻaʻole wale ka hōʻike ʻana i ka maikaʻi maikaʻi akā loaʻa pū kekahi i nā hopena ʻaoʻao o ka ʻōpū. Eia hou, ma ke ʻano he triple receptor agonist, ʻoi aku ka ikaika o ka hopena o ka pohō kaumaha o GLP-3 a me kahi ākea o nā heluna pili i hoʻohālikelike ʻia me nā lāʻau hoʻemi kaumaha hou.
He aha ka GLP-3?
ʻO GLP-3 kahi moʻolelo lōʻihi e hana ana i ka glucagon-like peptide-1 (GLP-1) receptor agonist. Hoʻololi ʻia a hoʻoponopono ʻia ma muli o ke ʻano o ka GLP-1 maoli, a hiki iā ia ke hoʻopaʻa a hoʻōla i ka mea hoʻokipa GLP-1, e hana ana i nā hana physiological e like me ka GLP-1 maoli, e like me ka hoʻoulu ʻana i ka huna ʻana o ka insulin, ke kāohi ʻana i ka huna ʻana o ka glucagon, ka hoʻopaneʻe ʻana i ka ʻōpū o ka ʻōpū, hoʻemi i ka makemake, etc.
He aha ke ʻano o ka hana a GLP-3?
ʻO ke ʻano o ka hana a GLP-3 mai kona hopena agonistic i nā mea loaʻa he nui. ʻO ka mea mua, hiki i kona hopena agonistic ma ka glucagon-like peptide-1 receptor (GLP-1R) ke hoʻonui i ka huna ʻana o ka insulin, kaohi i ka huna ʻana o ka glucagon, hoʻohaʻahaʻa 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 lawe ʻana i ka meaʻai [2] . ʻO ka lua, ʻo kona hopena agonistic ma 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 hoʻopilikia i ka metabolism momona, kaohi ʻana i ka lipolysis a me ka hoʻoulu ʻana i ka synthesis momona [2] . Eia kekahi, 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. Eia nō naʻe, ma lalo o ka hana a GLP-3, ua hoʻopau ʻia kēia hopena hoʻonui i ka glucose e nā hopena o nā mea hoʻokipa ʻelua ʻē aʻe, ʻoiai e hāpai ana i ka lipolysis a me ka hōʻemi ʻana i ka momona 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, ʻoiai ʻo ka hoʻoulu ʻana o GLP-1R a me GIPR e hoʻoikaika i ka huna ʻana o ka insulin a pale i ka huna ʻana o ka glucagon, a ua hoʻopau ʻia ka hoʻōla ʻana o GCGR 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 keʻano o ka hoʻohaʻahaʻaʻana i ka momona, hoʻonui ka GCGR i ka lipolysis a ho'ēmi i ka hoʻouluʻana o ka momona, aʻo ka hoʻouluʻana o GLP-1R e hoʻonui i ka satiety a ho'ēmi i kaʻaiʻana, e ho'ēmi i ka momona momona [1] . Eia kekahi, he hopena hoʻomaikaʻi ka 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.
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]
Ma nā ʻaoʻao hea e hōʻike ai ʻo GLP-3 i kona hopena?
Hōʻike ka GLP-3 i nā hopena koʻikoʻi ma nā ʻano he nui
Ka hopena pohō kaumaha: Ua hōʻike ʻo GLP-3 i nā hopena pohō kaumaha ma nā hoʻokolohua lapaʻau he nui. No ka laʻana, i loko o kahi noiʻi lapaʻau e pili ana i 338 mau mākua (Jastreboff AMM, 2023), ua loaʻa i nā mea maʻi i mālama ʻia me nā koina like ʻole o GLP-3 i ka pohō kaumaha nui ma 48 mau pule. Ma waena o lākou, ua nalowale nā mea maʻi i ka hui 12mg dose i 24.2% o ko lākou kaumaha kino, a he hapa nui o nā mea maʻi i loaʻa i ka pohō kaumaha i nā pae like ʻole. No ka laʻana, i waena o nā poʻe maʻi e loaʻa ana i ka 4mg, 8mg, a me 12mg doses, 92%, 100%, a me 100% o nā mea maʻi, kēlā me kēia, ua nalowale 5% a ʻoi aku paha o ko lākou kaumaha kino. Ma kekahi noiʻi ʻē aʻe [3] , ua hōʻike ʻia ʻelua mau hoʻokolohua i hoʻopaʻa ʻia e pili ana i 353 mau mea maʻi me ke ʻano 2 metabolism mellitus 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 pū i ka hemoglobin glycated (HbA1C). Eia kekahi, i nā hoʻokolohua o nā poʻe maʻi me ka momona me ka ʻole o ka metabolism, ua hoʻoiho ʻo GLP-3 i ka 24.2% o ka pohō kaumaha i nā maʻi, a ʻo 83% o nā mea maʻi i nalowale i ka 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.
Ka mālama ʻana i ke ʻano 2 metabolism mellitus: Hōʻike pū ʻia ʻo GLP-3 i kekahi mau mea hiki ke mālama i ka type 2 metabolism mellitus. 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 mea maʻi me ke ʻano 2 metabolism mellitus, ua hōʻike ʻo GLP-3 i nā hopena koʻikoʻi o ka hoʻokele glucose koko. Hoʻohālikelike ʻia me ka placebo, ua emi iho ka hemoglobin glycated e 1.64% [3] . Eia kekahi, i ka hoʻāʻo randomized, double-blind, placebo and active-controlled parallel-group phase 2 hoʻāʻo, nā ʻano holoholona me ka type 2 metabolism mellitus, ma hope o ka loaʻa ʻana o ka lāʻau GLP-3, ua hōʻike i kahi emi nui o nā pae hemoglobin glycated, a ua emi pū ke kaumaha o ko lākou kino ma ke ʻano o ka hopena . Hiki ke hoʻopili ʻia kēia i nā hopena piha o ka lāʻau lapaʻau ma GLP-1, GCGR, a me GIPR, ka mea 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 mālama ʻana i ka glucose i ke koko i nā maʻi me ka metabolism, a laila e hōʻemi ana i ka hopena o nā pilikia cardiovascular [3, 5, 6].
Lapaʻau ʻana i ka maʻi ʻaʻai momona ʻole (NAFLD): ʻO GLP-3 he peptide agonist triple receptor hou 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 momona momona ʻole. I loko o kahi noiʻi, ua mālama ʻia kahi hoʻokolohua hoʻāʻo ʻia, ʻelua makapō, placebo-controlled hoʻāʻo no 48 mau pule ma luna o nā poʻe i komo me ka 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 pili i ka momona o ka ate mai ka baseline i nā poʻe i mālama ʻia me nā ʻano like ʻole o GLP-3 (1mg, 4mg, 8mg, a me 12mg) ʻo -42.9%, -57.0%, -81.4%, a me -82.4%, i kēlā me kēia, ʻoiai i 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 hoʻoponopono i ka metabolism kanaka mai nā ʻāpana he nui ma o ka hoʻoulu ʻana i ka glucagon receptor, glucose-dependent insulinotropic polypeptide receptor, a me glucagon-like peptide-1 receptor, 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 ua lawe mai i nā koho lapaʻau hou no nā poʻe maʻi me ka momona, type 2 metabolism mellitus, a me nā mea ʻē aʻe.
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].
