Los ntawm Cocer Peptides 
15 hnub dhau los
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.
Txheej txheem cej luam
Maz yog ib qho tshuaj tshiab uas ua raws li ob tus agonist ntawm glucagon-zoo li peptide-1 (GLP-1) thiab glucagon receptors. GLP-1 thiab glucagon receptors ua lub luag haujlwm tseem ceeb hauv kev tswj cov metabolism hauv tib neeg lub cev. GLP-1 feem ntau yog tso tawm los ntawm L hlwb hauv txoj hnyuv, tso tawm tom qab noj mov, thiab txhawb nqa cov insulin tso tawm hauv cov piam thaj hauv cov ntshav thaum inhibiting glucagon secretion, yog li txo qis cov ntshav qabzib. GLP-1 tseem ua rau lub plab zom mov qeeb, ua rau kom satiety, thiab txo cov zaub mov noj, yog li pab tswj qhov hnyav. Glucagon receptors feem ntau tswj cov ntshav qabzib sib npaug. Tom qab glucagon khi rau nws cov receptors, nws ua rau muaj ntau txoj hauv kev los txhawb glycogenolysis thiab gluconeogenesis, yog li ua kom cov ntshav qabzib nce ntxiv. Maz, raws li ib tug dual agonist, ua tiav cov kev cai metabolic los ntawm ib tug ntse synergistic mechanism.
Mechanism ntawm Action
Ntshav Glucose Regulation Mechanism
Txhawb nqa Insulin Secretion: Tom qab khi rau GLP-1 receptor, Maz qhib txoj hauv kev qis qis, suav nrog cAMP-PKA txoj kev taw qhia. Kev ua kom txoj hauv kev no txhim kho qhov rhiab ntawm pancreatic β-hlwb rau cov piam thaj, ua rau kev txhim kho ntawm cov tshuaj insulin gene qhia thiab nce insulin synthesis thiab secretion. Thaum cov ntshav qabzib nce siab, Maz tuaj yeem ua kom muaj txiaj ntsig zoo ntawm cov tshuaj insulin, yog li txo qis cov ntshav qabzib. Hauv cov neeg mob uas muaj hom 2 metabolic, Maz nce postprandial insulin secretion los ntawm cov txheej txheem no, pab tswj cov ntshav qabzib kom ruaj khov.
Inhibition ntawm glucagon secretion: Maz qhov kev ua ntawm glucagon receptors kuj cuam tshuam glucagon secretion. Los ntawm kev khi rau glucagon receptors, nws inhibits teeb liab hloov pauv hauv pancreatic α hlwb, txo glucagon synthesis thiab tso tawm. Qhov no inhibits glycogenolysis thiab gluconeogenesis, txo cov piam thaj ntau lawm ntawm qhov chaw thiab pab ntxiv kom txo cov ntshav qabzib. Qhov kev tswj hwm ob ntawm insulin thiab glucagon secretion ua rau Maz muaj txiaj ntsig zoo hauv kev tswj cov ntshav qabzib, ua kom muaj kev tswj hwm cov ntshav qabzib ntau dua thiab zam kev hloov pauv loj.
Cov feem pua ntawm cov kev hloov pauv ntawm lub hauv paus hauv lub cev hnyav dhau sijhawm. Tus nqi ntawm cov neeg koom mus txog qhov hnyav poob lub hom phiaj.
Qhov hnyav tswj mechanism
Kev tswj kev noj qab haus huv: Maz khi rau GLP-1 receptors, ua kom cov neurons nyob rau hauv lub chaw tswj kev noj qab haus huv hypothalamic. Cov neurons no koom rau hauv kev sib kis ntawm satiety signals, thiab Maz qhov kev ua kom cov teeb liab no, yog li txo cov khoom noj. Nws kuj tseem tuaj yeem cuam tshuam rau kev tso tawm ntawm cov tshuaj hormones hauv plab hnyuv, xws li ghrelin, ntxiv kev tswj kev qab los noj mov. Hauv kev sim tshuaj, cov neeg koom nrog siv Maz qhia txog kev noj qab haus huv thiab txo qis noj zaub mov txhua hnub, ua rau poob phaus.
Kev siv hluav taws xob ntau ntxiv: Maz kuj tseem tuaj yeem txhawb kev poob phaus los ntawm kev cuam tshuam lub cev lub zog metabolism. Kev tshawb fawb qhia tias nws tuaj yeem qhib cov ntaub so ntswg adipose, ua rau nws cov kev ua haujlwm thermogenic. Brown adipose cov ntaub so ntswg yog nplua nuj nyob rau hauv mitochondria thiab tuaj yeem siv lub zog los ntawm cov thermogenesis uas tsis yog tshee. Maz tuaj yeem tswj hwm txoj hauv kev cuam tshuam los txhawb kev sib txawv thiab ua kom cov xim av adipocytes, txhim kho lawv lub peev xwm thermogenic, yog li ua kom lub cev siv zog thiab ua kom poob phaus. Maz kuj tseem tuaj yeem cuam tshuam cov metabolism ntawm cov nqaij dawb adipose, txhawb kev hloov pauv ntawm cov rog dawb rau cov rog xim av, ntxiv dag zog rau cov rog metabolism thiab txo cov rog.
Uric acid tswj mechanism
Gene qhia kev tswj hwm: Hauv kev tshawb fawb siv tus qauv nas ntawm hyperuricemia, kev hloov pauv tseem ceeb hauv kev qhia ntawm qee cov noob tseem ceeb tau pom tom qab Maz cuam tshuam. Cov kev hloov pauv hauv cov noob caj noob ces tuaj yeem ua tiav qhov txo qis hauv qib uric acid los ntawm kev tswj hwm cov txheej txheem ntawm uric acid synthesis thiab koom nrog cov txheej txheem xws li glycolipid metabolism thiab purine metabolism. Upregulated genes txhawb uric acid excretion los yog koom nyob rau hauv metabolic txoj kev uas inhibit uric acid synthesis, thaum downregulated noob txo cov synthesis ntawm precursors rau uric acid synthesis, yog li comprehensively txo cov ntshav uric acid theem.
Kev tswj cov txheej txheem metabolic: Kev soj ntsuam ntawm lub raum transcriptomics qhia tias Maz cuam tshuam ua rau muaj txiaj ntsig zoo ntawm KEGG txoj hauv kev suav nrog cov kua tsib tso tawm, cov kab mob renin-angiotensin, histidine metabolism, platinum tsis kam, hematopoietic cell lineages, ntxiv, thiab coagulation cascade. Kev tswj hwm txoj hauv kev no tuaj yeem cuam tshuam ncaj qha rau uric acid metabolism. Kev tswj cov kua tsib txoj hauv kev tuaj yeem cuam tshuam rau cov kua tsib acid metabolism, uas cuam tshuam nrog lipid metabolism. Kev hloov pauv hauv lipid metabolism tuaj yeem cuam tshuam rau uric acid ntau lawm thiab tso tawm. Kev tswj hwm ntawm renin-angiotensin system tuaj yeem cuam tshuam rau lub raum hemodynamics thiab tubular muaj nuj nqi, yog li cuam tshuam rau uric acid reabsorption thiab excretion.
Kev ua tau zoo
Glucose Control nyhuv
Hauv randomized, ob-dig muag, placebo-tswj Theem 2 kev soj ntsuam hauv cov neeg mob uas muaj hom 2 metabolism, Maz tau pom cov txiaj ntsig tseem ceeb ntawm cov ntshav qabzib tswj. Txoj kev tshawb no tau muab cov neeg laus uas muaj hom 2 metabolism kom tau txais 3 mg, 4.5 mg, lossis 6 mg ntawm Maz, 1.5 mg ntawm qhib-label dulaglutide, lossis placebo, thiab muab cov tshuaj subcutaneous rau 20 lub lis piam. Cov txiaj ntsig tau pom tias los ntawm lub hauv paus pib mus rau lub lim tiam 20, qhov kev hloov pauv ntawm hemoglobin A1c (HbA1c) hauv Maz pawg muaj li ntawm -1.41% txog -1.67%, thaum pawg dulaglutide tau hloov pauv -1.35% thiab cov placebo pawg tau hloov pauv ntawm 0.03%. Piv nrog rau cov placebo pab pawg, cov kev hloov pauv hauv HbA1c qib hauv txhua pawg Maz koob tshuaj yog qhov tseem ceeb (tag nrho P <0.0001). Qhov no qhia tias Maz muaj txiaj ntsig zoo dua li cov placebo hauv kev txo qis HbA1c qib hauv cov neeg mob uas muaj hom 2 metabolism, thiab piv rau lossis txawm tias zoo dua rau dulaglutide. Qhov txo qis hauv qib HbA1c qhia txog Maz lub peev xwm los txhim kho kev tswj glycemic mus sij hawm ntev hauv cov neeg mob, yog li txo qhov tshwm sim ntawm cov teeb meem mob ntshav qab zib.
Cov teebmeem poob phaus
Maz qhia tau hais tias muaj txiaj ntsig zoo hauv kev tswj qhov hnyav. Hauv kev tshawb fawb tsom rau cov neeg laus rog rog lossis rog rog, 24 lub lis piam ntawm Maz kev kho mob pom tau tias muaj txiaj ntsig zoo. Cov neeg laus rog rog (lub cev hnyav index [BMI] ≥24 kg/m²) nrog polyphagia thiab/lossis tsawg kawg yog ib qho kev rog rog, lossis cov neeg rog rog (BMI ≥28 kg/m²), tau muab tso rau (3: 1: 3: 1: 3: 1) kom tau txais kev kho mob txhua lub limtiam Maz 3mg, 6 mg, 4 mg. Cov txiaj ntsig tau pom tias los ntawm lub hauv paus rau lub lim tiam 24, qhov feem pua ntawm qhov hnyav yog -6.7% (tus qauv yuam kev 0.7) hauv Maz 3 mg pawg, -10.4% (0.7) hauv pawg 4.5 mg, -11.3% (0.7) hauv pawg 6 mg, thiab 1.0% qhov chaw (0.7) hauv pawg. Piv nrog rau cov placebo, qhov sib txawv ntawm kev kho mob rau Maz thoob plaws txhua pawg koob tshuaj yog li ntawm -7.7% txog -12.3% (tag nrho P <0.0001). Qhov no qhia tau hais tias Maz tuaj yeem txo lub cev hnyav hauv cov neeg laus rog rog lossis rog rog hauv kev noj tshuaj ntau dua. Qhov kev poob phaus no tsis tsuas yog pab txhim kho cov neeg mob lub cev zoo nkaus li tab sis tseem ceeb dua txo cov kev pheej hmoo ntawm ntau yam kab mob rog, xws li kab mob plawv thiab cov metabolism.
Uric acid txo cov nyhuv
Nyob rau hauv tus qauv nas ntawm hyperuricemia, Maz pom zoo uric acid-txo cov teebmeem. Hyperuricemia tau tshwm sim hauv cov nas los ntawm kev tswj hwm qhov ncauj ntawm adenine thiab potassium oxinic acid, tom qab ntawd los ntawm kev kho mob nrog ntau koob tshuaj Maz. Cov txiaj ntsig tau pom tias cov pab pawg nruab nrab thiab koob tshuaj ntau ntawm Maz (0.05 mg / kg thiab 0.075 mg / kg, tswj hwm los ntawm kev txhaj tshuaj subcutaneous txhua 3 hnub) txo qis cov ntshav uric acid (SUA) qib hauv cov nas. Maz kuj txhim kho lub raum ua haujlwm, txo cov ntshav creatinine (SCr) thiab cov zis protein (U-Pro), thiab txhim kho lub raum cov ntaub so ntswg pathology. Qhov no qhia tias Maz tsis tsuas yog txo cov ntshav uric acid, tab sis kuj muaj kev tiv thaiv lub raum puas los ntawm hyperuricemia.
Cov cheeb tsam thov
Kev kho mob hom 2 Metabolism
Muab Maz qhov ua tau zoo hauv kev tswj ntshav qabzib, nws tuav lub peev xwm zoo rau kev siv hauv kev kho mob hom 2 metabolism. Tam sim no, kev kho mob ntawm hom 2 metabolism feem ntau yog nyob ntawm kev sib xyaw ntawm ntau yam tshuaj los tswj cov ntshav qabzib thiab tiv thaiv qhov tshwm sim ntawm cov teeb meem. Raws li tus tshiab dual receptor agonist, Maz lub cim tshwj xeeb ntawm kev ua haujlwm ua rau nws tswj cov piam thaj metabolism hauv ntau qib, muab kev kho tshiab rau cov neeg mob uas muaj hom 2 metabolism. Piv nrog rau cov tshuaj antidiabetic ib txwm siv, Maz tsis tsuas yog txo cov ntshav qabzib tab sis kuj muaj txiaj ntsig ntawm kev txo qhov hnyav, tshwj xeeb tshaj yog rau cov neeg mob ntshav qab zib hom 2 uas rog dhau lossis rog.
Kev rog rog thiab tswj kev rog rog
Kev rog rog thiab rog dhau los ua teeb meem kev noj qab haus huv thoob ntiaj teb uas cuam tshuam nrog qhov pib ntawm ntau yam kab mob. Maz cov teebmeem tseem ceeb hauv kev tswj qhov hnyav ua rau nws muaj peev xwm kho tau rau cov neeg rog thiab rog rog. Los ntawm kev tswj hwm kev qab los noj mov thiab nce kev siv hluav taws xob, Maz tuaj yeem pab cov neeg rog rog thiab rog rog kom poob phaus thiab txhim kho lawv cov txheej txheem metabolic. Piv nrog rau cov kev poob phaus xws li kev noj zaub mov thiab kev tawm dag zog, Maz muaj kev xaiv kev kho mob zoo dua, tshwj xeeb tshaj yog rau cov neeg uas tawm tsam kom ua tiav lawv qhov hnyav tshaj plaws los ntawm kev cuam tshuam kev ua neej. Tsis tas li ntawd, vim nws cov txheej txheem ntawm kev nqis tes ua cuam tshuam nrog ntau yam kev tswj hwm lub cev, Maz tuaj yeem muaj txiaj ntsig zoo ntawm cov hlab plawv thiab cov kab mob metabolic thaum txo qhov hnyav, yog li txo qis kev pheej hmoo ntawm kev rog rog.
Xaus
Hauv cov ntsiab lus, raws li tus tshiab dual agonist ntawm GLP-1 thiab glucagon receptors, Maz qhia cov txheej txheem tshwj xeeb ntawm kev ua thiab kev ua haujlwm tseem ceeb hauv kev tswj ntshav qabzib, tswj qhov hnyav, thiab muaj peev xwm tswj hwm uric acid, ua lub luag haujlwm tseem ceeb hauv kev tswj hwm hom 2 metabolism, rog, thiab rog dhau.
Qhov chaw
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[3] Ji L, Jiang H, Chen Z, et al. Ib theem 2 randomized tswj kev sim ntawm mazdutide hauv Suav cov neeg rog rog lossis cov neeg laus uas rog rog [J]. Nature Communications, 2023,14(1):8289.DOI:10.1038/s41467-023-44067-4.
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Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
