Na Cocer Peptides 
18 mau lā aku nei
ʻO nā ʻatikala a me nā ʻike huahana i hāʻawi ʻia ma kēia pūnaewele pūnaewele wale nō no ka hoʻolaha ʻana i ka ʻike a me nā kumu hoʻonaʻauao.
ʻO nā huahana i hāʻawi ʻia ma kēia pūnaewele i manaʻo wale ʻia no ka noiʻi in vitro. Hana ʻia ka noiʻi in vitro (Latin: *i ke aniani*, ʻo ia hoʻi i ka ipu aniani) ma waho o ke kino kanaka. ʻAʻole kēia mau huahana he lāʻau lapaʻau, ʻaʻole i ʻae ʻia e ka US Food and Drug Administration (FDA), a ʻaʻole pono e hoʻohana ʻia no ka pale ʻana, mālama, a hoʻōla paha i kekahi maʻi olakino, maʻi, a i ʻole maʻi. Ua pāpā loa ʻia e ke kānāwai ke hoʻokomo i kēia mau huahana i loko o ke kino kanaka a holoholona paha ma kekahi ʻano.
Ka nānā 'ana o Triple Agonists
I nā makahiki i hala iho nei, me ka hohonu o ka noiʻi ʻana i ka pathogenesis o nā maʻi metabolic, ua lilo ka hoʻomohala ʻana i nā lāʻau agonist multi-target e kuhikuhi ana i nā mea loaʻa hormone he nui. ʻO Retatrutid kahi mea hou triple agonist o ka glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), a me ka glucagon (GC) receptors.
(1) Physiological Kumu o ka Hormone Receptor Functions
ʻO ka GIP Receptor: ʻO GIP kahi hormone huna huna insulin i loko o ka ʻōpū i hoʻokuʻu ʻia ma hope o ka ʻai ʻana. Ma ka hoʻopaʻa ʻana i ka mea loaʻa GIP, hoʻoulu ʻo GIP i ka huna ʻana o ka insulin, a ʻo kēia hopena stimulatory e pili ana i ka glucose, ʻo ia hoʻi i ka piʻi ʻana o ke kiʻekiʻe o ke koko, hoʻonui ʻo GIP i kāna hopena huna huna insulin, e kōkua ana i ka mālama ʻana i nā pae glucose koko paʻa. Hoʻohui ʻia, komo ʻo GIP i ka hoʻoponopono ʻana i ka lipid metabolism, ka hopena i ka ʻokoʻa adipocyte a me ka hōʻiliʻili lipid.
Fig. 1. Hoʻemi ka lapaʻau RETA a i ʻole SEMA i ke kaumaha o ke kino a hoʻomaikaʻi i ka glucose koko hoʻokēʻai. b, Epididymal keʻokeʻo adipose paona i helu ʻia ma ka hopena. c Ua helu ʻia ka glucose koko hoʻokē ʻai ma ka pae kumu a ma ke aʻo ʻana i nā manawa i hōʻike ʻia a hiki i ka hopena. d Ua hōʻike ʻia ka hoʻopaʻa ʻia ʻana o ka tumo a i ʻole 'ka lawe ʻana i ka maʻi.'
GLP-1 receptor: Ua huna ʻia ʻo GLP-1 e nā pūnaewele L intestinal a loaʻa pū kekahi hopena insulinotropic pili i ka glucose, hoʻonui i ka synthesis a me ka hoʻokuʻu ʻana o ka insulin, kaohi ʻana i ka huna ʻana o ka glucagon, a me ka hōʻemi ʻana i ka hoʻopuka glucose hepatic. Hoʻopaneʻe pū ʻo GLP-1 i ka hoʻokaʻawale ʻana o ka ʻōpū, hoʻonui i ka māʻona, a no laila e hōʻemi ana i ka ʻai ʻana. Loaʻa iā ia nā hopena pale a me ka proliferative i nā cell beta pancreatic, e kōkua ana i ka mālama ʻana i ka hana pancreatic.
3. GC mea hoʻokipa:
Ma hope o ka hoʻopaʻa ʻana i ka mea loaʻa GC, hana nui ka glucagon i ke ake ma o ka hoʻolaha ʻana i ka glycogenolysis a me ka gluconeogenesis, a laila e hoʻokiʻekiʻe ai i nā pae glucose koko. I ka lipid metabolism, hoʻoikaika ia i ka lipolysis, hoʻonui i ka hoʻokuʻu ʻana a me ka oxidation o nā momona momona no ka ikehu. Ma lalo o nā kūlana physiological maʻamau, ua pāpā ʻia ka huna ʻana o ka glucagon i ka wā e piʻi ai ke kiʻekiʻe o ka glucose koko e mālama i ke kaulike glucose.
(2) Pono o Triple Agonist Action
Ma ke ʻano he triple agonist, hiki i ka Retatrutid ke hoʻoikaika i kēia mau mea hoʻokipa ʻekolu, e hana ana i nā hopena synergistic. Ma ka hoʻoulu ʻana i nā mea loaʻa GIP a me GLP-1, hoʻonui ia i ka huna ʻana o ka insulin i hilinaʻi i ka glucose, ʻoi aku ka maikaʻi o ka hoʻohaʻahaʻa ʻana i nā pae glucose koko. ʻO ka hoʻonui ʻana o ka māʻona a me ka lohi ʻana o ka ʻōpū o ka ʻōpū i hoʻoulu ʻia e ka GLP-1 receptor activation, me ka lipolysis i hāpai ʻia e ka GC receptor activation, hui pū i ka hoʻokele kaumaha. Hāʻawi kēia ʻano hana i manaʻo nui ʻia i kahi hoʻoponopono ʻoi aku ka piha o nā kaʻina pathophysiological like ʻole e pili ana i nā maʻi metabolic.
Mechanism of Action of Retatrutid in Metabolic Diseases
ʻO nā maʻi metabolic kahi papa o nā kūlana i hoʻopilikia ʻia i nā kaʻina metabolic i loko o ke kino, me nā maʻi maʻamau e like me ka maʻi maʻi, ka momona, a me ka maʻi momona momona ʻole. Hoʻohana ʻo Retatrutid i kāna mau hopena i kēia mau maʻi metabolic ma o kāna mau waiwai triple agonist.
(1) Mechanism of Action in Diabetes
Hoʻoponopono Glucose: Hoʻoulu ʻo Retatrutid i nā mea loaʻa GIP a me GLP-1, e hoʻonui ana i ka huna ʻana o ka insulin i hilinaʻi i ka glucose. Ke piʻi aʻe ke kiʻekiʻe o ka glucose i ke koko, ʻoi aku ka maikaʻi o ka hoʻoulu ʻana i nā cell beta pancreatic e hūnā i ka insulin, e hoʻoikaika ana i ka lawe ʻana a me ka hoʻohana ʻana i ka glucose, a laila e hoʻohaʻahaʻa i nā pae glucose koko. Ma ka pale ʻana i ka huna ʻana o ka glucagon a me ka hōʻemi ʻana i ka hoʻopuka ʻana o ka glucose hepatic, hoʻopaʻa hou ia i nā pae glucose koko. Ma nā hoʻokolohua lapaʻau e pili ana i nā poʻe maʻi me ka maʻi diabetes type 2, ʻo ka mālama ʻana iā Retatrutid i hopena i ka hoʻemi nui ʻana i nā pae glucose koko hoʻokēʻai a me ka postprandial.
Ka pale ʻana i nā pūnaewele beta pancreatic: ʻO ka hoʻāla ʻana o ka mea hoʻokipa GLP-1 ʻaʻole wale e hoʻolaha i ka huna ʻana o ka insulin akā he hopena pale a proliferative hoʻi i nā cell beta pancreatic. Hiki i ka Retatrutid ke hoʻokō i kēia ma ka hoʻoikaika mau ʻana i ka mea loaʻa GLP-1, hoʻolohi i ka apoptosis cell beta, hoʻonui i kā lākou helu a me ka hana, a laila e hoʻomaikaʻi ai i ka hiki ke huna ʻana i ka insulin a me ka mālama ʻana i nā pae glucose koko paʻa i ka wā lōʻihi.
(2) Mechanism of action in obesity
Hoʻoponopono i ka hoʻohana ʻana i ka ikehu: Hoʻoulu ʻo Retatrutid i nā mea loaʻa GLP-1, hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū, hoʻolōʻihi i ka manawa paʻa o ka ʻai i loko o ka ʻōpū, hoʻonui i ka māʻona, a hoʻemi i ka ʻai ʻana i ka meaʻai. Hiki iā ia ke hana ma ke kikowaena o ke kikowaena e hoʻoponopono i nā neurotransmitters pili i ka makemake, e like me ke kāohi ʻana i ka hoʻokuʻu ʻana o ka orexin, e hōʻemi hou ana i ka ʻai, a ma laila e kāohi ai i ka lawe ʻana i ka ikehu.
Hoʻonui i ka hoʻonui ʻana i ka ikehu: Hoʻoulu ʻia ka GC receptor i ka lipolysis, hoʻonui i ka hoʻokuʻu ʻana a me ka oxidation o nā momona momona no ka hana ikehu. Hāʻawi ka oxidation o nā momona momona i ka ikehu i ke kino, hōʻemi i ka mālama ʻana i ka momona, a kōkua i ka pohō kaumaha. Hoʻokomo pū ka hoʻoulu ʻana o ka mea loaʻa GIP i ka hoʻoponopono ʻana i ka ikehu metabolism, e hoʻonui ana i ka hoʻolilo ikehu.
Helu 2 Hoʻemi ka lāʻau RETA i ke kaumaha o ke kino a me ka adiposity, hoʻomaikaʻi i ka glucose koko hoʻokē ʻai. Hōʻike ʻia ka hoʻololi pākēneka o ke kaumaha o ke kino mai ka pae kumu. b Ua kaupaona ʻia ka ʻiʻo adipose keʻokeʻo epididymal ma ka hopena a hoʻohālikelike ʻia i ka nui o ke kaumaha o ke kino. c Ua helu ʻia ka glucose koko hoʻokē ʻai ma ka pae kumu a ma ke aʻo ʻana i nā manawa i hōʻike ʻia a hiki i ka hopena.
(3) Mechanism of action in non-alcoholic fatty ate maʻi
Hoʻomaikaʻi i ka metabolism lipid hepatic: Hoʻoulu ʻo Retatrutid i ka GC receptor, e hāpai ana i ka haki ʻana a me ka β-oxidation o ka momona i loko o ke ake, a laila e hōʻemi ana i ka hōʻiliʻili momona i loko o ke ake. ʻO ka hoʻoulu ʻana o ka GIP a me GLP-1 receptors hiki ke hoʻoponopono i ka hōʻike ʻana o nā genes e pili ana i ka metabolism lipid i loko o ke ake, e hoʻonui i ka hōʻike ʻana o nā mea lawe ʻawaʻawa momona a me nā oxidases waikawa momona, e hoʻoikaika ai i ka lawe ʻana a me ka oxidation, a hoʻomaikaʻi hou i ka metabolism lipid hepatic.
Hoʻonui i ka ʻike insulin: ʻOiai e hoʻomaikaʻi ana i ka hoʻoponopono glucose a me ka hoʻonui ʻana i ka huna ʻana o ka insulin, hiki iā Retatrutid ke hoʻonui i ka ʻike insulin hepatic ma o ka hoʻoulu ʻana i nā mea loaʻa GLP-1. Hoʻonui ka naʻau o ka insulin i ka pane ʻana o ke ake i ka insulin, ʻoi aku ka maikaʻi o ka pale ʻana i ka hoʻopuka ʻana o ka glucose hepatic, e hōʻemi ana i ka synthesis fatty acid de novo, a ma laila e hoʻēmi ai i ka steatosis hepatic.
Nā noi a me nā hopena o Retatrutid i nā maʻi Metabolic
(1) Nā noi no ka maʻi diabetes
lycemic Control Effects: Hōʻike ʻo Retatrutid i nā hopena mana glycemic koʻikoʻi i nā maʻi me ka maʻi diabetes type 2. Wahi a ka ʻikepili, ua hōʻike ka poʻe maʻi i mālama ʻia me Retatrutid i kahi hōʻemi nui o ka pae hemoglobin A1c (HbA1c). I loko o kahi ho'āʻo i hoʻopaʻa ʻia e pili ana i 353 mau maʻi me ka maʻi diabetes type 2, ua emi nā pae HbA1c i ka hui lapaʻau Retatrutid e 1.64% mai ka papa kuhikuhi, ʻoiai ʻaʻohe loli nui i ka hui placebo.
Hoʻohālikelike me nā lāʻau lapaʻau ʻē aʻe: Ke hoʻohālikelike ʻia me nā lāʻau antidiabetic kuʻuna e like me ka metformin a i ʻole GLP-1 receptor agonists, hōʻike ʻo Retatrutid i nā hopena hoʻomalu glucose koko.
(2) Hoʻohana i ka momona
Nā hopena o ke kaumaha: Hōʻike ka Retatrutid i ka maikaʻi nui i ka mālama ʻana i ka momona. I nā hoʻokolohua lapaʻau e kuhikuhi ana i nā poʻe maʻi obese makua, ua ʻike ʻia ka pohō kaumaha nui ma hope o 48 mau pule o ka mālama ʻana me nā ʻano like ʻole o Retatrutid. Ma hoʻokahi hoʻāʻo, ua ʻike nā maʻi i mālama ʻia me ka 12mg dose o Retatrutid i ka awelika o ke kaumaha o 24.2% ma hope o 48 mau pule, hoʻohālikelike ʻia me 2.1% wale nō i ka hui placebo. Eia hou, 83% o ka poʻe i komo i ka hui kiʻekiʻe-dose i loaʻa i ke kaumaha o 15% a ʻoi aku paha, ʻoi aku ma mua o ka helu 2% ma ka hui placebo.
Nā hopena lōʻihi: Mālama maikaʻi ʻo Retatrutid i nā hopena o ke kaumaha i loko o ka wā mālama. Hōʻike kēia i ka hoʻohana lōʻihi hiki ke kōkua i ka mālama ʻana i ke kaumaha paʻa a pale i ka loaʻa hou ʻana o ke kaumaha, kahi mea e pono ai no ka mālama lōʻihi o ka momona.
(3) Hoʻohana i ka maʻi ʻaʻai momona ʻole
ʻO ka hoʻemi ʻana i ka momona o ka ate: I nā poʻe maʻi me ka metabolic dysfunction-pili i ka maʻi momona a me ka momona o ka ate ≥10%, ʻo ka mālama ʻana i ka Retatrutid i hopena i kahi hōʻemi nui o ka momona o ka ate. I loko o ka randomized, double-blind, placebo-controlled trial, ma 24 mau pule, ua emi iho ka momona o ke akepaa e 81.4% a me 82.4% mai ka papa kuhikuhi i ka 8 mg a me 12 mg mau hui, i kela mea keia mea, aʻo ka placebo pūʻulu piʻi ma ka 0.3% wale nō.
ʻO nā pono a me ka hiki o ka Triple Agonist
Hoʻoponopono piha ʻo Retatrutid i nā ala pathophysiological he nui o nā maʻi metabolic ma o ka hoʻoulu ʻana i ka GIP, GLP-1, a me GC mau mea loaʻa. Mai ka mālama ʻana i ka glucose koko, ka mālama ʻana i ke kaumaha, i ka hoʻomaikaʻi ʻana i ka metabolism lipid hepatic, ua hāʻawi kēia ʻano hana manaʻo nui i ka hoʻoponopono ʻana i nā maʻi metabolic i hoʻohālikelike ʻia i nā lāʻau lapaʻau hoʻokahi, e hōʻike ana i ka hiki ke hoʻoponopono i ka etiology paʻakikī o nā maʻi metabolic. Hōʻike nā ʻikepili hoʻokolohua lapaʻau i kēia manawa ua loaʻa ʻo Retatrutid i nā hopena koʻikoʻi i ka mālama ʻana i nā maʻi metabolic e like me ka maʻi diabetes, ka momona, a me ka maʻi momona momona ʻole.
Ka hopena
Ma ke ʻano he triple agonist hou, paʻa ʻo Retatrutid i ka hoʻohiki no ka mālama ʻana i nā maʻi metabolic.
Nā kumu
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[4] Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutid no ka Obesity - A Phase 2 Trial[J]. New England Journal of Medicine, 2023,389(6):514-526.DOI:10.1056/NEJMoa2301972.
[5] ʻO Doggrell SA. ʻO ka retatrutide (LY3437943), he GLP-1, GIP, a me ka glucagon receptor agonist kahi hana i mua i ka mālama ʻana i ka maʻi diabetes a me ka momona? [J]. Manaʻo Manaʻo no nā lāʻau noiʻi, 2023,32(5):355-359.DOI:10.1080/13543784.2023.2206560.
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