GLP-3 10 mg

▎ GLP-3 Structure

▎ GLP-3 Kev Tshawb Fawb

Dab tsi yog qhov kev tshawb fawb keeb kwm ntawm GLP-3?

Kev rog rog yog ib qho teeb meem loj rau pej xeem noj qab haus huv niaj hnub no. Kev rog dhau tuaj yeem ua rau muaj ntau yam teeb meem kev noj qab haus huv, xws li hom 2 metabolism, kab mob plawv, ntshav siab, dyslipidemia, thiab kab mob siab tsis muaj dej cawv. Nrog rau kev nce ntxiv ntawm qhov tshwm sim ntawm kev rog, muaj kev xav tau ntau ntxiv rau cov kev kho tshiab uas tuaj yeem tswj hwm lub cev hnyav thiab txhim kho kev noj qab haus huv ^[1] . Txawm hais tias kev hloov pauv txoj kev ua neej, xws li kev ua kom lub cev thiab txo kev noj zaub mov, yog thawj txoj hauv kev rau kev tswj hwm qhov hnyav, kev saib xyuas mus sij hawm ntev ntawm kev poob phaus tseem yog qhov nyuaj rau ntau tus neeg laus. GLP-3 yog ib qho tshiab triple receptor agonist uas ua haujlwm ntawm glucagon-zoo li peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), thiab glucagon receptor (GCGR). Qhov no multi-receptor mechanism ntawm kev txiav txim muab nws tshwj xeeb zoo hauv kev poob phaus. Piv nrog rau cov tshuaj poob phaus uas ua rau ntawm ib qho receptor, GLP-3 tuaj yeem tswj hwm lub cev cov txheej txheem metabolic ^[1] . GLP-3 ua tiav qhov hnyav los ntawm kev tswj hwm ntau yam tshuaj hormones receptors. Nws tsis tsuas yog muaj qhov hnyav hnyav tab sis kuj muaj cov kev mob tshwm sim me me hauv plab hnyuv. Tsis tas li ntawd, piv nrog rau lwm cov tshuaj poob phaus tshiab, GLP-3, raws li triple receptor agonist, muaj qhov hnyav dua qhov hnyav dua thiab ntau dua ntawm cov neeg siv.

GLP-3 mechanism ntawm kev txiav txim yog dab tsi?

Cov txheej txheem ntawm kev ua ntawm GLP-3 feem ntau tshwm sim los ntawm nws cov teebmeem agonistic ntawm ntau tus receptors. Ua ntej, nws cov nyhuv agonistic ntawm glucagon-zoo li peptide-1 receptor (GLP-1R) nce insulin secretion, inhibits glucagon secretion, txo cov ntshav qabzib, thiab tib lub sijhawm qeeb plab hnyuv, nce satiety, thiab txo cov zaub mov noj ^[2] . Qhov thib ob, nws cov nyhuv agonistic ntawm cov piam thaj-dependent insulinotropic polypeptide receptor (GIPR) tuaj yeem txhawb kev tsim cov tshuaj insulin, txhim kho kev siv cov piam thaj, thiab muaj kev cuam tshuam rau cov roj metabolism, inhibiting lipolysis thiab txhawb kev rog rog ^[2] . Tsis tas li ntawd, txawm hais tias cov nyhuv agonistic ntawm GLP-3 ntawm glucagon receptor (GCGR) feem ntau txhawb nqa glycogenolysis thiab gluconeogenesis hauv daim siab, nce ntshav qabzib ntau ntau, raws li kev ua ntawm GLP-3, cov nyhuv ntawm cov ntshav qabzib nce ntxiv yog offset los ntawm cov teebmeem ntawm ob lub receptors. Nyob rau tib lub sijhawm, nws txhawb lipolysis thiab txo cov rog rog ^[2] . Qhov ntau hom phiaj ntawm qhov kev txiav txim no tuaj yeem ua tau zoo dua hauv kev kho mob rog dua li ib leeg receptor agonists.

Los ntawm tib lub sijhawm ua rau peb cov receptors no, GLP-3 tuaj yeem siv ntau yam kev tswj hwm cov metabolism thiab tsim cov teebmeem kev noj qab haus huv ntawm kev rog thiab cov kab mob ntsig txog. Nyob rau hauv cov nqe lus ntawm kev tswj cov ntshav qabzib ntau ntau, vim yog kev ua haujlwm ntawm GLP-1R thiab GIPR txhawb kev tsim cov tshuaj insulin thiab inhibiting glucagon secretion, thiab kev ua kom GCGR raug cuam tshuam los ntawm cov teebmeem ntawm ob lub receptors, GLP-3 tuaj yeem tswj cov ntshav qabzib zoo, uas yog qhov tseem ceeb rau kev kho mob, hom 2 metabolism ^[1] . Nyob rau hauv cov nqe lus ntawm kev txo cov rog tsub zuj zuj, qhov ua rau ntawm GCGR txhawb lipolysis thiab txo cov rog tsub zuj zuj. Nyob rau tib lub sijhawm, qhov ua rau GLP-1R nce satiety thiab txo cov khoom noj, ntxiv txo cov rog synthesis ^{[1, 2]} . Tsis tas li ntawd, GLP-3 kuj tseem muaj txiaj ntsig zoo rau cov kab mob uas tsis yog-alcoholic fatty siab. Nws tuaj yeem txo cov rog hauv daim siab thiab txhim kho daim siab ua haujlwm. Ib qho randomized, ob-dig muag, kev sim tshuaj placebo tau pom tias qhov nruab nrab ntawm cov txheeb ze hloov pauv hauv daim siab rog hauv pab pawg kho mob GLP-3 ntawm 24 lub lis piam tau qis dua li hauv pawg placebo ^[3].

HbA1c, lub cev hnyav, ntshav siab, thiab lipids Cov ntaub ntawv yog qhov tsawg tshaj plaws-squares txhais tau tias (nrog cov kab yuam kev uas qhia SEs) los ntawm kev tsom xam cov txiaj ntsig, tshwj tsis yog sau tseg.

Source: PubMed ^[4]

Yuav ua li cas raws nraim GLP-3 tswj cov piam thaj metabolism tom qab ua kom peb receptors?

GLP-3 tswj cov ntshav qabzib los ntawm ntau lub tswv yim, suav nrog kev ua kom GLP-1 thiab GIP receptors, txhawb kev tsim cov tshuaj insulin, inhibiting glucagon secretion, qeeb plab hnyuv, tswj cov roj metabolism, thiab txo qis ANGPTL3/8 qib. Raws li kev tswj hwm cov ntshav qabzib, GLP-3 ua haujlwm ntawm GLP-1 thiab GIP receptors, txhawb kev nkag siab ntawm pancreatic β hlwb rau cov piam thaj, ua ke thiab tso tawm insulin, thiab tom qab ntawd txhawb kev nce thiab siv cov piam thaj los ntawm cov ntaub so ntswg, ua tiav cov txiaj ntsig ntawm kev txo cov ntshav qabzib hauv cov neeg mob ntshav qab zib hom ^2. Kev txo qis glycated hemoglobin (HbA1c), uas feem ntau tau txais txiaj ntsig los ntawm nws lub luag haujlwm hauv stimulating insulin secretion (Rosenstock J, 2023). Nyob rau tib lub sijhawm, ua kom cov GLP-1 receptor tuaj yeem cuam tshuam qhov tso tawm ntawm glucagon los ntawm pancreatic α hlwb, tiv thaiv cov ntshav qabzib kom siab dhau. Hauv kev tshawb fawb soj ntsuam, nws tau pom tias cov qib glucagon ntawm cov neeg mob uas siv GLP-3 tau txo qis, uas ua rau kom muaj kev ruaj ntseg ntawm cov ntshav qabzib ^{[4, 5]} . Ua kom muaj GLP-1 thiab GIP receptors tuaj yeem ncua sijhawm ntawm lub plab zom mov, ua kom lub plab zom mov thiab nqus cov zaub mov, thiab txo qis qhov nce siab hauv cov ntshav qabzib tom qab. Cov kev tshawb fawb pom tau hais tias lub sij hawm ntawm lub plab khoob ntawm cov neeg mob kho nrog GLP-3 yog qhov ntev heev tom qab noj mov, yog li txo qis tus nqi ntawm cov ntshav qabzib tom qab ^[4].

Kev tswj hwm cov roj metabolism los ntawm GLP-3 kuj tseem cuam tshuam rau cov piam thaj metabolism. Piv txwv li, hauv kev tshawb fawb ntawm cov neeg mob rog rog, nws tau pom tias GLP-3 tuaj yeem txo qis triglycerides (TG), low-density lipoprotein (LDL), thiab low-density lipoprotein (VLDL) cholesterol ^{[2, 6]} . Qhov kev txhim kho hauv lipid metabolism tuaj yeem cuam tshuam nrog kev txhim kho ntawm insulin rhiab heev, yog li pab tswj cov ntshav qabzib. Tshwj xeeb, tom qab kev kho GLP-3, plasma 3-hydroxybutyric acid (3-HB) nce, nrog rau kev nce hauv 3-hydroxybutyrylcarnitine (C ₄OH), qhov sib piv ntawm acetylcarnitine rau dawb carnitine (C ₂/ C ₀), thiab nruab nrab-chain acylcarnitine lipolysis ntawm cov ntaub so ntswg muaj zog.

GLP-3 tuaj yeem txo tag nrho cov dihydroceramides (DhCers), thiab qhov kev hloov pauv no cuam tshuam nrog kev txhim kho insulin rhiab heev, txo cov hepatic steatosis, thiab cov kab mob hauv lub cev ^{[6] .Tam sim no, GLP-3 tuaj yeem txo cov concentration ntawm ANGPTL3/8 complex hauv cov ntshav ntawm hom 2 metabolism hauv cov neeg mob,} tswj cov piam thaj ⁷ . ANGPTL3/8 yog qhov zoo tshaj plaws circulating inhibitor ntawm lipoprotein lipase (LPL), thiab nws cov qib ntshav muaj feem cuam tshuam ncaj qha rau TG thiab qis lipoprotein cholesterol (LDL-C). GLP-3 txo qis ANGPTL3/8, uas tuaj yeem tswj cov piam thaj metabolism los ntawm kev txo qis triglyceride-nplua nuj lipoproteins ^[7] .

GLP-3 qhia txog qhov cuam tshuam li cas?

Qhov tseem ceeb yuag poob nyhuv: 

GLP-3 tau qhia txog qhov hnyav hnyav hauv ntau qhov kev sim tshuaj. Piv txwv li, hauv kev tshawb fawb soj ntsuam nrog 338 tus neeg laus ^[2] , cov neeg mob kho nrog ntau koob tshuaj GLP-3 tau poob qhov hnyav ntawm 48 lub lis piam. Ntawm lawv, cov neeg mob hauv pawg koob tshuaj 12mg tau poob qis ntawm 24.2%, thiab feem ntau ntawm cov neeg mob tau poob phaus mus rau qhov sib txawv. Piv txwv li, ntawm cov neeg mob tau txais 4mg, 8mg, thiab 12mg koob, 92%, 100%, thiab 100% ntawm cov neeg mob poob 5% lossis ntau dua ntawm lawv lub cev hnyav, raws li. Hauv lwm txoj kev tshawb fawb ^[8] , ob qhov kev sim tswj kev sib tw nrog 353 hom 2 cov neeg mob metabolism tau pom tias piv nrog cov placebo, GLP-3 tuaj yeem txo lub cev hnyav ntawm cov neeg mob los ntawm 11.89kg thiab txo glycated hemoglobin (HbA1C). Tsis tas li ntawd, hauv kev sim ntawm cov neeg laus uas tsis muaj ntshav qab zib rog rog, GLP-3 ua rau poob phaus ntawm 24.2% hauv cov neeg mob, thiab 83% ntawm cov neeg mob poob 15% lossis ntau dua ntawm lawv lub cev hnyav ntawm 48 lub lis piam. Cov txiaj ntsig no qhia tau tias GLP-3 muaj peev xwm loj hauv kev poob phaus.

Kev kho mob ntawm hom 2 metabolism : 

GLP-3 kuj tseem qhia tau qee qhov peev xwm hauv kev kho mob ntawm hom 2 metabolism. Hauv qee qhov kev sim tshuaj, GLP-3 tau pom tias txo qis hauv glycated hemoglobin (HbA1c) thiab kev poob phaus raws li koob tshuaj. Piv txwv li, hauv ib txoj kev tshawb fawb, hauv cov neeg mob ntshav qab zib hom 2, GLP-3 tau pom muaj txiaj ntsig zoo ntawm cov ntshav qabzib, txo glycated hemoglobin los ntawm 1.64% piv nrog cov placebo ^{[4, 8]} . Tsis tas li ntawd, nyob rau hauv ib qho randomized, ob-dig muag, placebo, thiab active-tswj parallel-paj pawg theem 2 mus sib hais, tsiaj cov qauv nrog hom 2 metabolism tau pom qhov txo qis hauv glycated hemoglobin qib thiab cov koob tshuaj raws li qhov hnyav tom qab tau txais kev kho GLP-3 ^[4] . Qhov no tuaj yeem raug ntaus nqi los ntawm cov txiaj ntsig zoo ntawm cov tshuaj ntawm GLP-1, GCGR, thiab GIPR, uas txhim kho cov piam thaj metabolism thiab lub zog sib npaug.

Kev txhim kho ntawm cov teeb meem plawv plawv: 

GLP-3 tuaj yeem tsis tsuas yog txo lub cev hnyav xwb tab sis kuj txhim kho cov kab mob plawv, xws li ntshav lipid profile thiab glycated hemoglobin qib. Qhov no qhia tau hais tias muaj kev sib raug zoo ntawm kev sib raug zoo ntawm kev rog thiab cov kab mob plawv, thiab GLP-3 tuaj yeem txhim kho cov hlab plawv kev noj qab haus huv ntawm cov neeg mob rog dhau los ntawm ntau txoj hauv kev. Piv txwv li, txo qis HDL-C, apoB, thiab LDLP qib tuaj yeem txo qhov kev pheej hmoo ntawm atherosclerosis; txo glycated hemoglobin qib tuaj yeem txhim kho cov ntshav qabzib tswj hauv cov neeg mob metabolism, yog li txo qis kev pheej hmoo ntawm cov teeb meem plawv ^[8-10] .

Kev kho mob uas tsis yog-alcoholic fatty siab kab mob (NAFLD): 

GLP-3 yog ib qho tshiab triple receptor agonist peptide uas tsom rau glucagon receptor (GCGR), qabzib-dependent insulinotropic polypeptide receptor (GIPR), thiab glucagon-zoo li peptide-1 receptor (GLP-1R). Cov kev tshawb fawb tau pom tias GLP-3 muaj peev xwm kho tau cov kab mob uas tsis yog-alcoholic fatty siab. Hauv ib txoj kev tshawb fawb, ib qho randomized, ob-dig muag, kev sim tshuaj placebo kav ntev li 48 lub lis piam tau ua rau cov neeg koom nrog metabolic dysfunction-associated fatty siab kab mob thiab lub siab rog cov ntsiab lus ntawm ≥10%. Cov txiaj ntsig tau pom tias ntawm 24 lub lis piam, qhov nruab nrab hloov pauv hauv daim siab rog piv rau lub hauv paus hauv cov neeg koom nrog kev kho mob sib txawv ntawm GLP-3 (1mg, 4mg, 8mg, thiab 12mg) yog -42.9%, -57.0%, -81.4%, thiab -82.4%, feem, thaum nyob hauv pawg placebo yog +0.3% ^[3 ] Qhov no qhia tau hais tias GLP-3 tuaj yeem muaj kev kho mob tseem ceeb ntawm cov kab mob tsis muaj dej cawv fatty siab.

Hauv kev xaus, raws li tus tshiab triple receptor agonist, GLP-3 qhia tau hais tias muaj peev xwm loj hauv kev kho mob rog thiab lwm yam kab mob. Nws tuaj yeem qhib lub glucagon receptor, qabzib-nyob ntawm insulinotropic polypeptide receptor, thiab glucagon-zoo li peptide-1 receptor, kev tswj hwm lub cev metabolism los ntawm ntau qhov ntev, txhim kho ntshav qabzib tswj, txo lub cev hnyav, thiab tswj cov lipid metabolism. Qhov tshwm sim ntawm GLP-3 coj cov kev kho mob tshiab rau cov neeg mob rog rog, hom 2 metabolism, thiab lwm yam kab mob. Nws yuav tsum tau ua txhaum los ntawm cov kev txwv ntawm ib txwm siv tshuaj receptor agonist, muab riam phom muaj zog dua los daws cov teeb meem loj zuj zus ntawm kev rog thiab cov kab mob metabolic, txhawb kev txhim kho ntxiv ntawm kev kho mob, txhim kho lub neej zoo ntawm cov neeg mob, thiab txo cov kev mob nkeeg hauv zej zog.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Rosenstock J yog tus kws tshawb fawb muaj txiaj ntsig zoo hauv kev kho mob, sib koom tes nrog cov koom haum xws li University of Texas Southwestern Medical Center thiab University of Texas Dallas. Nws kuj ua kev tshawb fawb ntawm cov chaw xws li Canadian VIGOR Center thiab Veloc Clin Res Ctr Med City. Nws txoj kev tshawb fawb nthuav dav endocrinology thiab cov metabolism, cov hlab plawv thiab cov hlab plawv, pharmacology, thiab kev sim tshuaj, nrog rau kev tsom mus rau cov metabolism, rog rog, thiab lwm yam kev kho mob thiab kev txhim kho tshuaj. J Rosenstock tau ua tiav cov txiaj ntsig tseem ceeb hauv cov tshuaj kho mob, tau raug hu ua Tus Kws Tshaj Lij Tshaj Lij Tshaj Lij Tshaj Lij los ntawm 2017 txog 2024. Qhov no qhia txog qhov cuam tshuam loj thiab kev lees paub dav ntawm nws txoj haujlwm. Los ntawm kev koom tes nrog ntau lub koom haum tshawb fawb, nws tau ua tiav cov txiaj ntsig kev tshawb fawb hauv kev tshawb fawb hauv kev siv tshuaj kho mob, tau txais txiaj ntsig zoo rau cov neeg mob metabolic thiab kab mob plawv thiab nce qib kev kho mob. Rosenstock J tau teev nyob rau hauv kev siv ntawm cov ntaub ntawv pov thawj [4].

▎ Cov Lus Qhia Tseem Ceeb

[1] Kaur M, Misra S. Kev tshuaj xyuas cov tshuaj tshawb nrhiav GLP-3, tus neeg sawv cev tshiab triple agonist rau kev kho mob rog rog [J]. European Journal of Clinical Pharmacology, 2024,80(5):669-676.DOI:10.1007/s00228-024-03646-0.

[2] Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-hormone-Receptor Agonist GLP-3 rau Obesity-A Phase 2 Trial [J]. New England Journal of Medicine, 2023,389(6):514-526.DOI:10.1056/NEJMoa2301972.

[3] Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist GLP-3 rau metabolic dysfunction-associated steatotic daim siab kab mob: ib theem randomized 2a sim [J]. Nature Medicine, 2024,30(7):2037-2048.DOI:10.1038/s41591-024-03018-2.

[4] Rosenstock J, Frias J, Jastreboff AM, et al. GLP-3, GIP, GLP-1 thiab glucagon receptor agonist, rau cov neeg uas muaj hom 2 metabolism: ib qho randomised, ob-dig muag, placebo thiab active-tswj, parallel-pab pawg, theem 2 sim ua nyob rau hauv teb chaws USA [J]. Lancet, 2023,402(10401):529-544.DOI:10.1016/S0140-6736(23)01053-X.

[5] Brzozowska P, Frańczuk A, Nowińska B, et al. GLP-3 - revolutionary nyuam qhuav tsim GLP agonist - cov ntaub ntawv tshuaj xyuas[J]. Zoo hauv Kev Ua Si, 2024.DOI: 10.12775/qs.2024.15.52125.

[6] Pirro V, Pearson MJ, Lin Y, et al. Cov teebmeem ntawm Triple-hormone Receptor Agonist GLP-3 ntawm Lipid Profiling hauv Cov Neeg Koom Nrog Kev rog [J]. Diabetes, 2024,73.DOI:10.2337/db24-117-OR.

[7] Wen Y, Lemen D, Chen Y, et al. Kev txo qis ntawm triglyceride-nplua nuj lipoproteins nrog GLP-3 hauv hom 2 metabolism tuaj yeem piav qhia los ntawm kev txo qis hauv ANGPTL3 / 8 qib [J]. European Heart Journal, 2024,45.DOI:10.1093/eurheartj/ehae666.2862.

[8] Lopez DC, Pajimna JT, Milan MD, et al. 7792 Kev Ua Tau Zoo ntawm GLP-3 rau Kev Txom Nyem thiab Nws Cov Teebmeem Cardiometabolic Ntawm Cov Neeg Laus: Kev Ntsuam Xyuas Txheej Txheem thiab Meta-Analysis[J]. Phau ntawv Journal of the Endocrine Society, 2024,8(1):163-749.DOI:10.1210/jendso/bvae163.749.

[9] Nicholls S, Pirro V, Lin Y, et al. Triple-hormone receptor agonist GLP-3 txhim kho lipoprotein thiab apolipoprotein profiles hauv cov neeg koom nrog rog lossis rog [J]. European Heart Journal, 2024,45.DOI:10.1093/eurheartj/ehae666.1501.

[10] Ray A. GLP-3: triple incretin receptor agonist rau kev tswj kev rog [J]. Cov Lus Qhia Txog Kev Tshawb Fawb Txog Tshuaj, 2023,32(11): 1003-1008.DOI: 10.1080/13543784.2023.2276754.

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.