Los ntawm Cocer Peptides 
13 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 ntawm GLP-1
GLP-1 yog ib qho tshiab glucagon-zoo li peptide-1 receptor agonist (GLP-1 RA). Glucagon-zoo li peptide-1 (GLP-1) yog cov tshuaj hormones ib txwm tso tawm los ntawm tib neeg lub cev uas ua lub luag haujlwm tseem ceeb hauv kev tswj ntshav qabzib. Thaum cov ntshav qabzib nce siab, GLP-1 yog zais cia thiab tswj cov ntshav qabzib los ntawm ntau yam txheej txheem. Txawm li cas los xij, hauv cov neeg mob ntshav qab zib, GLP-1 secretion feem ntau tsis txaus lossis nws cov teebmeem tsis txaus. GLP-1 khi rau GLP-1 receptors, ua raws li cov kev xav ntawm lub cev ntawm GLP-1, yog li ua rau muaj kev kho mob rau cov metabolism thiab tswj qhov hnyav.
Daim duab 1 Kev kho mob rau kev rog rog thiab lawv qhov cuam tshuam rau kev poob phaus
Lub luag haujlwm ntawm GLP-1 hauv Kev Kho Mob Ntshav Qab Zib
Txhawb nqa Insulin secretion
Nyob rau hauv cov xwm txheej ntawm lub cev, thaum cov ntshav qabzib nce siab, cov hlwb enteroendocrine hauv cov hnyuv secrete GLP-1. GLP-1 khi rau GLP-1 receptors nyob rau saum npoo ntawm pancreatic β hlwb, ua kom muaj ntau txoj hauv kev los ua kom cov insulin secretion. GLP-1 tseem tuaj yeem khi tshwj xeeb rau GLP-1 receptors ntawm qhov chaw ntawm pancreatic β hlwb, txhawb kev tsim cov tshuaj insulin hauv cov piam thaj hauv cov ntshav. Qhov no txhais tau hais tias thaum cov ntshav qabzib nce siab, GLP-1 txhawb nqa cov tshuaj insulin kom txo cov ntshav qabzib; Thaum cov ntshav qabzib nyob rau hauv qhov qub, nws cov txiaj ntsig ntawm kev txhawb nqa cov tshuaj insulin tsis muaj zog, yog li txo qis kev pheej hmoo ntawm hypoglycemia. Cov kev tshawb fawb tau pom tias tom qab kev kho mob nrog GLP-1, cov neeg mob cov tshuaj insulin secretion nce ntau, thiab cov ntshav qabzib tuaj yeem tswj tau zoo.
Daim duab 2: Ib txoj hauv kev nce qhov hnyav-centric piv rau qhov qis qis dua, qabzib-centric, thiab cardiometabolic mus kom ze. Incretin-raws li kev kho mob twb tau ua haujlwm nyob rau theem siab tshaj plaws.
Tsis zoo li cov tshuaj insulin secretagogues, xws li sulfonylureas, uas txuas ntxiv txhawb cov tshuaj insulin tsis hais txog cov ntshav qabzib thiab yuav ua rau muaj kev pheej hmoo ntawm hypoglycemia, GLP-1's glucose-concentration-dependent insulin secretion muaj peev xwm ua kom nws txo qis cov ntshav qabzib thaum txo qis qhov tshwm sim ntawm hypoglycemia.
Inhibition ntawm glucagon secretion
Glucagon yog ib yam tshuaj uas tso tawm los ntawm pancreatic α hlwb uas ua rau cov ntshav qabzib nce siab, ua haujlwm tsis zoo rau insulin. Hauv cov neeg mob ntshav qab zib, glucagon secretion feem ntau tseem nyob twj ywm tsis muaj kev txwv txawm tias cov ntshav qabzib nce siab. GLP-1 ua rau GLP-1 receptors ntawm pancreatic α hlwb los inhibit glucagon secretion. Thaum glucagon secretion txo qis, lub siab lub siab glycogenolysis thiab cov txheej txheem gluconeogenesis raug cuam tshuam, txo qis cov piam thaj endogenous thiab txo cov ntshav qabzib ntxiv. Cov kws tshawb fawb tau lees paub tias hauv cov neeg mob ntshav qab zib hom 2 tau kho nrog GLP-1, plasma glucagon qib txo qis, txo qis cov piam thaj hauv siab thiab ua lub luag haujlwm tseem ceeb hauv kev tswj cov ntshav qabzib.
Ncua lub plab khoob
GLP-1 ua rau GLP-1 receptors hauv plab hnyuv kom qeeb plab hnyuv. Kev ua pa sai sai ua rau cov zaub mov nkag mus rau hauv cov hnyuv sai sai, ua rau cov ntshav qabzib nce sai. Los ntawm kev ncua lub plab khoob, cov zaub mov tseem nyob hauv lub plab ntev dua thiab nkag mus rau hauv cov hnyuv me qeeb qeeb, ua rau kom maj mam nqus cov piam thaj ntau dua thiab tiv thaiv kom tsis txhob muaj cov piam thaj hauv cov ntshav nce ntxiv. Cov nyhuv no pab tswj cov ntshav qabzib hauv cov ntshav qabzib ruaj khov thiab txo cov ntshav qabzib hloov pauv. Hauv qee qhov kev sim tshuaj, cov neeg mob kho nrog GLP-1 tau ntsib qhov txo qis hauv cov ntshav qabzib tom qab peaks thiab cov ntshav qabzib me me hloov pauv, txhim kho cov ntshav qabzib tag nrho. Tsis tas li ntawd, kev ua rau lub plab zom mov qeeb tuaj yeem ua rau muaj kev nkag siab ntawm kev ua kom puv, pab txo qis kev noj zaub mov thiab yog li pab tswj cov ntshav qabzib thiab tswj qhov hnyav los ntawm lwm lub kaum sab xis.
Daim duab 3: Mechanism of GLP-1 for the Management of Obesity
Txhim kho β-Cell Function
Mob hyperglycemia tuaj yeem ua rau mob pancreatic β hlwb, ua rau kev ua haujlwm tsis zoo. GLP-1 tsis tsuas yog txo cov ntshav qab zib los ntawm kev txhawb nqa cov tshuaj insulin, tab sis kuj tseem tiv thaiv thiab kho cov kab mob pancreatic β hlwb, yog li txhim kho β cell. Cov kev tshawb fawb tshawb fawb tau pom tias GLP-1 tuaj yeem ua rau qee yam kev qhia hauv lub cev los txhawb β-cell proliferation, inhibit β-cell apoptosis, yog li ua kom cov lej thiab kev ua haujlwm ntawm β-hlwb. Hauv kev sim tsiaj txhu thiab qee qhov kev tshawb fawb soj ntsuam, nws tau pom tias tom qab siv GLP-1, lub peev xwm ntawm cov tshuaj insulin secretion ntawm β hlwb tau txhim kho, thiab cov tshuaj insulin kuj tau txhim kho. Qhov no yog qhov tseem ceeb heev rau kev kho mob mus sij hawm ntev ntawm hom 2 metabolism, vim nws pab ua kom cov kab mob qeeb qeeb thiab txo qhov kev pheej hmoo ntawm kev mob ntshav qab zib.
Kev siv GLP-1 hauv Kev Kho Mob Ntshav Qab Zib
GLP-1 muaj ntau txoj hauv kev hauv kev kho cov metabolism. Rau cov neeg mob ntshav qab zib hom 2 uas tau kuaj pom tshiab, yog tias cov ntshav qabzib tsis nce siab thiab tsis muaj teeb meem hnyav lossis lwm yam mob hnyav, monotherapy nrog GLP-1 tuaj yeem txiav txim siab. Cov kev tshawb fawb soj ntsuam pom tau hais tias qee cov neeg mob tshiab tau ntsib qhov txo qis hauv hemoglobin A1c (HbA1c) qib thiab poob phaus tom qab lub sijhawm ntawm kev kho mob monotherapy. Piv txwv li, hauv PIONEER series ntawm cov kev tshawb fawb, cov neeg mob kho nrog qhov ncauj GLP-1 monotherapy tau ntsib qhov txo qis hauv HbA1c qib piv rau cov placebo pab pawg, nrog kev nyab xeeb zoo thiab kev zam. Qhov zoo ntawm kev kho mob monotherapy yog tias nws zam qhov kev pheej hmoo ntawm kev siv tshuaj sib cuam tshuam nrog kev sib xyaw ua ke, thiab nws cov kev tswj hwm yooj yim pab txhim kho cov neeg mob ua raws li kev kho mob.
GLP-1 tuaj yeem siv ua ke nrog lwm cov tshuaj. Thaum ua ke nrog metformin, uas yog thawj kab tshuaj rau hom 2 metabolism, nws txhim kho insulin tsis kam thiab txo cov piam thaj hauv siab. Ob qho tshuaj muaj cov txheej txheem ua haujlwm ntxiv, ua kom muaj txiaj ntsig zoo ntawm cov ntshav qabzib. Cov kev tshawb fawb tau pom tias qhov kev sib xyaw ua ke no ua rau txo qis HbA1c ntau ntau thiab ua rau poob phaus ntau dua. Piv txwv li, hauv qee qhov kev sim tshuaj, cov neeg mob kho nrog metformin uas ntxiv GLP-1 tau ntsib kev txo qis hauv HbA1c ntau dua piv rau cov neeg uas txuas ntxiv metformin monotherapy, nrog rau kev poob phaus ntxiv, yam tsis muaj kev pheej hmoo ntawm hypoglycemia. Cov txheej txheem no tsim nyog rau cov neeg mob uas cov ntshav qabzib tsis tswj tau zoo nrog metformin monotherapy.
Rau cov neeg mob uas muaj hom 2 metabolism uas muaj ntshav qabzib ntau thiab xav tau kev kho tshuaj insulin, ntxiv GLP-1 rau kev kho tshuaj insulin tuaj yeem txo cov koob tshuaj insulin. Hauv kev kho tshuaj insulin, cov neeg mob feem ntau ntsib teeb meem xws li qhov hnyav nce thiab nce kev pheej hmoo ntawm hypoglycemia. Thaum siv ua ke, GLP-1 cov teebmeem ntawm kev txhawb nqa cov tshuaj insulin secretion thiab inhibiting glucagon secretion tuaj yeem txhim kho kev siv tshuaj insulin, txo cov koob tshuaj, thiab yog li txo qhov kev pheej hmoo ntawm qhov hnyav nce thiab hypoglycemia. Piv txwv li, hauv qee qhov kev tshawb fawb soj ntsuam, cov neeg mob uas tau ntxiv GLP-1 rau lawv txoj kev kho cov tshuaj insulin tau ntsib qhov kev txo qis hauv cov tshuaj insulin, nrog rau kev txo qis hauv HbA1c ntxiv, poob phaus, thiab txo qis hauv cov zaus ntawm hypoglycemia.
GLP-1 tuaj yeem siv ua ke nrog lwm cov tshuaj tiv thaiv kab mob xws li SGLT2 inhibitors. SGLT2 inhibitors txo cov ntshav qabzib los ntawm kev txhawb nqa cov kua nplaum tawm hauv cov zis. Kev sib xyaw ua ke ntawm ob tuaj yeem txhim kho kev tswj ntshav qabzib los ntawm cov txheej txheem sib txawv thiab kuj tseem tuaj yeem muaj kev sib koom ua ke hauv kev tswj qhov hnyav.
Lub luag haujlwm ntawm GLP-1 hauv kev tswj qhov hnyav
Kev tshaib plab
GLP-1 ua rau GLP-1 receptors hauv nruab nrab paj hlwb, tshwj xeeb hauv hypothalamus. Lub hypothalamus yog ib cheeb tsam tseem ceeb hauv lub cev rau kev tswj kev qab los noj mov thiab lub zog sib npaug. Tom qab khi rau GLP-1 receptors nyob rau hauv lub hypothalamus, GLP-1 tuaj yeem tswj cov kev tso tawm ntawm cov neuropeptides, xws li txo qis kev tso tawm ntawm neuropeptide Y (NPY), uas yog ib qho muaj zog qab los noj mov. Tsis tas li ntawd, GLP-1 tuaj yeem ua rau muaj kev ua haujlwm ntawm proopiomelanocortin (POMC) neurons, uas nws qhov kev ua kom muaj kev txaus siab. Los ntawm cov txheej txheem no, GLP-1 zoo txo qis qab los noj mov, ua rau cov neeg mob txo lawv cov khoom noj. Hauv kev sim tshuaj, cov neeg rog rog lossis rog rog siv GLP-1 qhia txog kev noj qab haus huv thiab kev noj zaub mov kom tsawg, tso lub hauv paus rau kev poob phaus.
Kev siv hluav taws xob ntau ntxiv
Ntxiv nrog rau kev txo qis qab los noj mov, GLP-1 kuj tseem tuaj yeem cuam tshuam lub zog metabolism, nce kev siv hluav taws xob. Kev tshawb fawb qhia tias GLP-1 tuaj yeem nce kev siv hluav taws xob los ntawm kev tswj hwm cov haujlwm ntawm cov ntaub so ntswg adipose. Brown adipose cov ntaub so ntswg yog ib hom tshwj xeeb ntawm cov nqaijrog uas nws lub luag haujlwm tseem ceeb yog siv lub zog los ntawm thermogenesis. GLP-1 tuaj yeem ua rau qee qhov kev taw qhia hauv cov ntaub so ntswg adipose, txhawb kev fatty acid oxidation thiab thermogenesis. Tsis tas li ntawd, GLP-1 tuaj yeem cuam tshuam lub zog metabolism hauv cov ntaub so ntswg xws li cov leeg, nce kev siv zog txawm tias so. Piv txwv li, hauv kev sim tsiaj, tom qab kev tswj hwm ntawm GLP-1, cov tsiaj cov metabolism hauv lub zog tau nce, thiab lawv lub cev qhov hnyav poob txawm tias thaum noj zaub mov tseem zoo ib yam, qhia tias GLP-1 ua lub luag haujlwm zoo hauv kev tswj qhov hnyav los ntawm kev siv zog nce ntxiv.
Kev tswj cov roj metabolism
GLP-1 kuj muaj kev tswj xyuas cov roj metabolism. Nws tuaj yeem txhawb kev tawg ntawm cov rog, txo cov rog synthesis, thiab inhibit cov roj cia. Hauv daim siab, GLP-1 tuaj yeem cuam tshuam kev ua haujlwm ntawm cov enzymes xws li fatty acid synthase, yog li txo cov fatty acid synthesis. Tsis tas li ntawd, nyob rau hauv cov ntaub so ntswg adipose, GLP-1 tuaj yeem txhawb kev rog rog, nce kev tso tawm ntawm cov fatty acids dawb, thiab pab txhawb lawv nkag mus rau hauv mitochondria rau oxidative tawg, yog li txo cov roj cia. Cov kev tshawb fawb soj ntsuam tau pom tias tom qab lub sijhawm kho nrog GLP-1, cov neeg mob lub cev rog cov ntsiab lus, tshwj xeeb tshaj yog cov roj visceral, txo qis. Qhov no tsis yog tsuas yog pab kom poob phaus xwb tab sis kuj muaj qhov cuam tshuam tseem ceeb rau kev txhim kho cov kab mob metabolic thiab txo txoj kev pheej hmoo ntawm cov kab mob plawv.
Daim ntawv thov ntawm GLP-1 hauv Kev Tswj Kev Nyuaj Siab
Rau cov neeg mob rog rog lossis rog rog nrog cov kab mob sib xws
GLP-1 muaj lub hom phiaj meej rau kev tswj hwm qhov hnyav. Rau cov neeg mob rog rog nrog BMI ≥30 kg / m² los yog cov neeg mob hnyav nrog BMI ≥27 kg / m² thiab tsawg kawg yog ib qho mob hnyav (xws li kub siab, hom 2 metabolism, lossis hypercholesterolemia), nws yog ib qho tshuaj tswj qhov hnyav. STEP series ntawm kev soj ntsuam kuaj pom pom qhov poob ceeb thawj hauv cov neeg mob kho. Hauv KAUJ RUAM 1 txoj kev tshawb fawb, cov neeg mob kho tau ua tiav qhov poob qis ntawm kwv yees li 15% dhau 68 lub lis piam, thaum pawg placebo poob tsuas yog li 2.4%. Cov txiaj ntsig no qhia tau hais tias nws tuaj yeem pab cov neeg rog rog lossis rog rog nrog cov xwm txheej cuam tshuam txog kev poob phaus tseem ceeb, txhim kho cov txiaj ntsig kev noj qab haus huv, thiab txo cov kev pheej hmoo ntawm kev rog rog.
Ua ke nrog kev ua neej nyob
Hauv kev tswj qhov hnyav, GLP-1 feem ntau yog siv ua ke nrog kev cuam tshuam kev ua neej, suav nrog txo qis calorie kom tsawg thiab ua kom lub cev ua si. Yog tias kev poob phaus tsuas yog siv tshuaj noj xwb yam tsis hloov pauv txoj kev ua neej tsis zoo, cov teebmeem feem ntau tsis muaj kev vam meej. Kev sib xyaw ua ke ntawm ob qho tib si muaj kev sib koom ua ke: cov tshuaj txo qis qab los noj mov thiab nce kev siv hluav taws xob, thaum tswj kev noj zaub mov kom tsawg calorie kom tsawg thiab ua kom lub cev muaj zog ntxiv ntxiv dag zog rau kev siv nyiaj, ua rau kom poob ceeb thawj ntau dua. Piv txwv li, hauv qee qhov kev kho mob, cov neeg mob uas ua raws li txoj kev npaj noj zaub mov tsawg uas tsim los ntawm kws noj zaub mov thiab nce lawv lub sijhawm ua haujlwm aerobic txhua lub lim tiam thaum tau txais kev kho mob tau txais txiaj ntsig zoo dua qhov hnyav dua li cov neeg uas vam khom rau kev noj tshuaj lossis kev ua neej nyob. Qhov kev sib koom ua ke no qhia txog qhov tseem ceeb ntawm kev tswj hwm kev tswj hwm qhov hnyav, pab cov neeg mob tsim kom muaj kev noj qab nyob zoo thiab ua tiav kev tswj qhov hnyav mus ntev.
Xaus
GLP-1 qhia tau tias muaj peev xwm tseem ceeb hauv kev kho cov metabolism thiab tswj qhov hnyav. Hauv kev kho cov metabolism, nws zoo tswj cov ntshav qabzib los ntawm ntau lub tswv yim, txhim kho β-cell muaj nuj nqi, thiab tuaj yeem siv los ua monotherapy lossis ua ke nrog lwm cov tshuaj tiv thaiv kab mob. Hauv kev tswj hwm qhov hnyav, nws txo qis qab los noj mov, nce kev siv hluav taws xob, thiab tswj cov roj metabolism, ua rau nws tsim nyog rau cov neeg rog rog lossis rog rog nrog cov xwm txheej cuam tshuam. Thaum ua ke nrog kev ua neej nyob, nws tau txais txiaj ntsig zoo dua.
Qhov chaw
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Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
