▎ GLP-2 ʻImi
He aha ke kumu noiʻi o GLP-2?
ʻO ka hoʻomohala ʻana o GLP-2, kahi lāʻau polypeptide synthetic, i hoʻokumu ʻia mai ka ʻike ʻana i nā palena o nā agonists receptor GLP-1 i ka mālama ʻana i ke ʻano 2 metabolism a me ka momona. ʻOiai ʻoi aku ka maikaʻi o ka GLP-1 receptor agonists i ka mālama ʻana i ka glucose koko a me ke kaumaha o ke kaumaha, ua ʻike nā ʻepekema i ko lākou nāwaliwali nāwaliwali o nā mea loaʻa GIP i kaupalena ʻia nā hopena therapeutic. No laila, ua manaʻo nā hui noiʻi e hoʻomohala i nā lāʻau lapaʻau hou e hiki ai ke hoʻāla i ka GIPR a me GLP-1R no ka hoʻokele glycemic piha a me ka hoʻokele kaumaha [1].
Ua mālama ʻia nā hoʻokolohua preclinical a me nā hoʻokolohua nui i ka wā o ka hoʻomohala ʻana.
Ua loiloi nā haʻawina holoholona preclinical i nā waiwai pharmacodynamic, e hōʻoia ana i kona hiki ke hoʻomalu i ka glycemic a me ka poho kaumaha. ʻO nā hoʻokolohua lapaʻau Phase I i loiloi mua i ka palekana, ka hoʻomanawanui, a me nā pharmacokinetics, e hōʻike ana i ka palekana maikaʻi.
a me ka hoʻomanawanui. Ua ʻimi hou nā hoʻāʻo ʻana o ka Phase II i ka pono a me ka palekana ma nā ʻano like ʻole i nā maʻi maʻi metabolism type 2, e hoʻoholo ana i nā pae hopena kūpono. ʻO nā hoʻokolohua Pivotal Phase III e like me ka SURPASS series, e pili ana i nā cohorts nui o nā mea maʻi metabolism type 2, ua hōʻike i ka GLP-2 i ʻoi aku ka maikaʻi o ka GLP-1 receptor agonists i ka hoʻohaʻahaʻa ʻana i ka glucose koko a me ke kaumaha, e hāʻawi ana i nā hōʻike ikaika no nā noi kūʻai ..
Hoʻokumu ʻia he 39 amino acids me nā hoʻololi hoʻololi e hoʻomaikaʻi i ke kūpaʻa a me ka pono, ua hoʻohui ʻia kona ʻano kūʻokoʻa i nā hana a GIP a me GLP-1 i loko o kahi mole hoʻokahi, e hoʻoulu ana i nā mea hoʻokipa hormone e pili ana i ka mana glycemic ma o nā mīkini ʻelua.
Ma ka lima hoʻokahi, hana ia ma ka pancreas e hoʻoikaika i ka huna ʻana o ka insulin a keʻakeʻa i ka hoʻokuʻu ʻana o ka glucagon no ka hoʻemi ʻana i ka glucose koko; ma ka ʻaoʻao ʻē aʻe, hana ia ma ke kikowaena o ka ʻōnaehana e hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū, hoʻonui i ka satiety, a hoʻemi i ka ʻai a me ka ʻai ʻana no ka mālama kaumaha. Hāʻawi kēia mīkini ʻelua i nā pono kūʻokoʻa GLP-2 i ka mālama ʻana i ke ʻano 2 metabolism a me ka momona, e hāʻawi ana i nā mea maʻi i nā koho therapeutic piha loa [1].
He aha ke ʻano o ka hana a GLP-2?
Hoʻohaʻahaʻa ʻo GLP-2 i ka glucose koko ma o nā hana he nui:
Hoʻoulu ʻia o nā mea hoʻokipa GLP-1: Hoʻopaʻa ʻia i nā mea loaʻa GLP-1 ma nā cell pancreatic β, hoʻohālike ia i ka GLP-1 kūlohelohe e hoʻoikaika i ka synthesis insulin, huna, a me ka ʻike glucose ʻoiai e hōʻemi ana i ka huna ʻana o ka glucagon e hoʻomaikaʻi i ka satiety a me ka hoʻopau ʻana i ka ʻai. I ka poʻe maʻi metabolism type 2, ʻo ka hoʻoulu ʻana i nā mea loaʻa GLP-1 e hoʻonui i ka huna ʻana o ka insulin no ka hoʻomaikaʻi ʻana i ka mana glycemic, ʻoiai ke kāohi nei i ka hoʻokuʻu ʻana o ka glucagon e hōʻemi hou i nā kumu glucose koko, e kōkua ana i ka hoʻoponopono glycemic [2].
Hoʻoulu ʻia o nā mea hoʻokipa GIP: Ke hana nei i nā mea loaʻa GIP, hoʻoulu ʻia ka hoʻoulu ʻana i ka ʻike insulin a me ka huna. Loaʻa nā mea loaʻa GIP i loko o nā ʻiʻo e like me nā pancreatic β cell, a me ka hoʻōla ʻana ma o nā ala hōʻailona intracellular e hoʻonui ai i ka huna ʻana o ka insulin a hoʻomaikaʻi i ka pane ʻana o ke kelepona i ka insulin no ka hoʻemi ʻana i ka glucose koko [2] . ʻO kēia agonism ʻelua receptor ka mea i ʻoi aku ka maikaʻi o ka GLP-2 i ka hoʻolaha ʻana i ka huna ʻana o ka insulin a me ka pale ʻana i ka hoʻokuʻu ʻana o ka glucagon ma mua o ka GLP-1 receptor agonists [2] .
Hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū a me ka māʻona nui: Hoʻopaneʻe ia i ka hoʻokuʻu ʻana o ka ʻōpū, hoʻolōʻihi i ka paʻa ʻana o ka meaʻai i loko o ka ʻōpū e hoʻolōʻihi i ka lawe ʻana i nā meaʻai a pale i ka piʻi ʻana o ka glucose koko postprandial. I kēia manawa, ʻo ka hana ʻana i ka ʻōnaehana nerve waena e hoʻonui i ka satiety e hōʻemi i ka makemake a me ka ʻai ʻana i ka meaʻai, ʻoi aku ka maikaʻi no ka momona i pili pinepine ʻia me ke ʻano 2 metabolism, e kōkua ana i ka hoʻomaikaʻi ʻana i ka insulin resistance a me ke kūlana metabolic holoʻokoʻa [3].
Hoʻomaikaʻi i ka Insulin Sensitivity a me Lipid Diabetes: Ke hoʻokiʻekiʻe ʻana i nā pae adiponectin - kahi mea momona momona e pili ana i ka ʻike insulin - kōkua i ka hoʻomaikaʻi ʻana i ka insulin sensitivity, e hiki ai i nā cell ke lawe maikaʻi a hoʻohana i ka glucose no ka hōʻemi ʻana i ke koko [2] (Anonymous, 2023). Hoʻomaikaʻi pū ia i nā profile lipid, me nā hopena palekana i ke olakino cardiovascular, ua hōʻike ʻia e hoʻomaikaʻi i ke koko a hoʻemi i ka LDL cholesterol a me nā triglycerides [3].
He aha nā haʻawina pili?
Hōʻike ʻo GLP-2 i ka maikaʻi nui i ka hoʻokele paona no nā mea maʻi obese a me ke ʻano 2 metabolism. Ma ka SURMOUNT-2 study, he Phase 3, double-blind, randomized, placebo-controlled trial i hanaʻia ma nā'āinaʻehiku, nā mākua i piha i ≥18 makahiki me BMI ≥27 kg / m² a me HbA1c 7-10% ua hoʻokaʻawale ʻia e loaʻa i kēlā me kēia pule subcutaneous GLP-2 (10 mg a i ʻole 15 mg) a i ʻole placebo no 72 pule. Ma ka wiki 72, ua −12.8% a me −14.7% ka nui o ka pohō kaumaha ma nā pūʻulu GLP-2 10 a me 15 mg me ka −3.2% ma ka hui placebo, me nā ʻokoʻa lapaʻau i manaʻo ʻia he −9.6 a me −11.6 pakeneka i hoʻohālikelike ʻia me ka placebo (p <10). Hoʻohui hou, ʻoi aku ka nui o nā maʻi i mālama ʻia ma GLP-2 i loaʻa i ka ≥5% pohō kaumaha (79-83% vs. 32%) (Garvey WT, 2023). Me ke kaumaha kumu kumu 100.7 kg, BMI 36.1 kg/m², a me HbA1c 8.02%, 72 mau pule o ka mālama ʻana me GLP-2 ʻaʻole wale i hoʻemi nui i ke kaumaha akā ua hoʻomaikaʻi ʻia ka mana glycemic [4] .
I ka hoʻomaikaʻi ʻana i ka neuropathy pili i ka metabolism, hōʻike ka noiʻi i nā GLP1-RA hiki ke hōʻemi i ka pilikia dementia i nā maʻi metabolism type 2 ma o ka hoʻomaikaʻi ʻana i ka hoʻomanaʻo, ke aʻo ʻana, a me ka lanakila ʻana i ka pilikia cognitive. Ma ke ʻano he GIP-RA / GLP-1RA ʻelua, ua aʻo ʻia ʻo GLP-2 i nā laina cell neuroblastoma (SHSY5Y) no kona hopena i ka ulu ʻana o neuronal (CREB a me BDNF), apoptosis (BAX / Bcl2 ratio), ʻokoʻa (pAkt, MAP2, GAP43, a me AGBL4), a me ke kūpaʻa o ka insulin (GLUT1, GLUT3UT4, a me S. Uaʻikeʻia e hoʻohana i nā hopena neuroprotective ma ka hoʻouluʻana i ke ala pAkt / CREB / BDNF a me nā hōʻailona hōʻailona lalo, e kū'ē i ka hyperglycemia- a me nā hopena pili i ka insulin ma ka pae neuronal. No laila, hiki i ka GLP-2 ke hoʻomaikaʻi i ka hyperglycemia-induced neurodegeneration a lanakila i ka pale ʻana o ka insulin neuronal, e hāʻawi ana i nā ʻike hou no ka mālama ʻana i ka neuropathy pili i ka metabolism [5].
Ma ke ʻano 2 metabolism lapaʻau holomua, GLP-2, he novel hypoglycemic lāʻau lapaʻau, ua lilo i ka mua apono 'alua GIP/GLP-1R agonist no ka metabolism i loko o ka US He nui nā ho'āʻo lapaʻau nui hōʻoia i kona nui glycemic-hoʻohaʻahaʻa a me ke kaumaha-lohia hopena, me ka hiki no ka cardiovascular pale. Ua wehe ka manaʻo o nā peptides synthetic i nā mea hiki ʻole i ʻike ʻia no GLP-2. Ke hoʻomau nei nā ho'āʻo a me nā hōʻike e hōʻike ana he lāʻau lapaʻau maikaʻi ia no ka maʻi hānai momona ʻole (NAFLD), ka pale renal, a me ka neuroprotection [6].
E pili ana i nā hopena lōʻihi i ke olakino cardiovascular, hiki i ka GLP-2 ke hōʻemi i ka pilikia o ka maʻi cardiovascular (CVD) ma o ka hoʻolaha ʻana i ka pohō kaumaha. Ua ʻike ʻia kahi haʻawina e nānā ana i ka hopena o GLP-2 i ka momona a me nā hanana CVD i nā pākeke US ma waena o ka poʻe kūpono no ka mālama ʻana i ka GLP-2, ua manaʻo ʻia ka 15 mg therapy e loaʻa i ka ≥15% a me ≥20% ka pohō kaumaha ma 70.6% a me 56.7% o nā pākeke, i ka unuhi ʻana i kahi hōʻemi o ka momona he 58.8%. I nā poʻe me ka CVD ʻole, ua emi mai ka 10-makahiki CVD pilikia mai 10.1% 'pre-treatment' a i 7.7% 'post-treatment,' e hōʻike ana i kahi hōʻemi loa o ka pilikia o 2.4% a me ka hōʻemi ʻana i ka pilikia o 23.6%, hiki ke pale i 2 miliona mau hanana CVD [7].
Ka hopena
I ka hōʻuluʻulu ʻana, ʻo GLP-2 kahi moʻolelo ʻelua agonist o GIP a me GLP-1 receptors, e paʻa ana i ka mea nui i ka mālama ʻana i ke ʻano 2 metabolism a me ka momona. Hoʻoikaika maikaʻi ia i ka huna ʻana o ka insulin, kaohi i ka hoʻokuʻu ʻana o ka glucagon, a hoʻoponopono pololei i ka glucose koko, e hōʻemi ana i nā pilikia hoʻopiʻi ʻoiai e hoʻomaikaʻi ana i ka hana pancreatic β-cell a me ka hoʻopaneʻe ʻana i ka holomua metabolism, me nā hopena cardioprotective. I ka mālama ʻana i ka momona, hoʻemi maikaʻi ia i ka ʻai ʻana i ka meaʻai, hoʻopau i ka ʻai, hoʻonui i ka māʻona, kōkua i ka hoʻemi ʻana i ke kaumaha, a hoʻohaʻahaʻa i nā pilikia pili i ka momona i ka wā e hoʻomaikaʻi ai i ka pale ʻana o ka insulin a me ka metabolism lipid. Hoʻohui ʻia, hōʻike ia i ka hiki ke mālama i nā maʻi metabolic e like me ka steatohepatitis non-alcoholic, sleep apnea syndrome, a me ka pau ʻole o ka naʻau, e hāʻawi ana i ka mālama piha ʻana ma o ka hoʻomaikaʻi ʻana i nā ʻāpana metabolic he nui. ʻO kāna papa kuhikuhi hoʻokahi pule i kēlā me kēia pule e hoʻonui i ka maʻalahi a me ka hoʻokō hoʻomanawanui. Ma ka mālama pono ʻana i ka glucose koko a me ke kaumaha, e hōʻemi ana i nā pilikia pilikia, a me ka hoʻomaikaʻi nui ʻana i ke kūlana kino, ka hana o kēlā me kēia lā, a me ka maikaʻi o ke ola, hoʻonui ʻo GLP-2 i ka hilinaʻi o ka poʻe maʻi i ka mālama ʻana i ka maʻi, hoʻēmi i nā kaumaha noʻonoʻo, a hoʻonui i ka hiki ke hoʻololi i ka nohona.
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
ʻO Kauka William T. Garvey he kanaka naʻauao kaulana a me ka mea noiʻi i hui pū ʻia me nā ʻoihana hanohano he nui, ʻo ia hoʻi ke Kulanui o Alabama ma Birmingham, Aston University, a me ka Birmingham Veterans Affairs Medical Center. ʻO kona ʻano hoʻonaʻauao a me kāna ʻike ʻoihana e pili ana i nā ʻano aʻoaʻo ākea i loko o ka lāʻau lapaʻau a me ka ʻepekema. Ua hāʻawi nui ʻo Kauka Garvey i nā ʻano o ka endocrinology a me ka metabolism, ka meaʻai a me ka meaʻai, ka biochemistry a me ka biology mole, a me ka lāʻau lapaʻau maʻamau a me loko, me ka nānā pono ʻana i ka ʻōnaehana cardiovascular a me ka cardiology. Ua ʻike nui ʻia a hoʻohanohano ʻia kāna hana, ʻoiai ua kapa ʻia ʻo ia he Highly Cited Researcher ma ka Cross-Field category no 2023 a me 2024, e hōʻike ana i ka hopena nui a me ka mana o kāna noiʻi ʻana i ke kaiāulu ʻepekema ākea.
Hoʻonui ʻia ko Kauka Garvey makemake noiʻi a me ka ʻike i nā ʻano like ʻole o nā maʻi metabolic a me kā lākou hoʻokele. Ua komo ikaika ʻo ia i ke aʻo ʻana i ka metabolism mellitus, ka momona, a me kā lākou mau pilikia pili, e manaʻo ana e wehe i nā hoʻolālā therapeutic novel a hoʻomaikaʻi i nā hopena maʻi. Hoʻopili ʻia kāna hana i ka noiʻi ʻepekema kumu, nā hoʻokolohua lapaʻau, a me nā noiʻi unuhi, e hoʻopaʻa ana i ka ʻokoʻa ma waena o nā ʻike noiʻi a me nā noi olakino honua maoli. Ma o kāna noiʻi nui, ua hāʻawi ʻo Kauka Garvey i ka ʻike hohonu ʻana i nā ʻano kumu o nā maʻi metabolic a ua kōkua i ke ʻano o nā alakaʻi alakaʻi a me nā protocol lapaʻau ma ke kahua o ka endocrinology a me ka metabolism. Ua helu ʻia ʻo Kauka William T. Garvey ma ka ʻōlelo kuhikuhi [4].
