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ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto famasitik, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
Ovaviu fɔ Tripul Agonist dɛn
insay di las ia, wit di dip we di risach de dip pan di pathogenesis fכ mεtabolik sik dεm, di divεlכpmεnt fכ mכlti-target agonist dεm we de tכk bכt mכltipכl כmon rεsεpכta dεm dεn bi wan hot tכpik. GLP-3 na nכvel tripl agonist fכ di glukכs-dipεndεnt insulinotropik pכlipεptida (GIP), glukagכn lεk pεptida-1 (GLP-1), εn glukagon (GC) rεsεpכta dεm.
(1) Fisiolכjik Bεsis fכ di Hכmon Risεptor Fכnshכn Dεm
GIP rεsεptor: GIP na כmon we de kכmכt na di intestinal insulin we di K sεl dεm na di sכmכl intestin de kכmכt, we de kכmכt kwik kwik wan afta dεn it. we i tay to di GIP risεptor, GIP de mek insulin sekreshכn, εn dis stimulatory ifekt de dipεnd pan glukכs, we min se as di bכdi glukכs lεvεl de go כp, GIP de εnhans in insulin-sekret ifekt, we de εp fכ mεnten di blכd glukכs lεvεl stebul. apat frכm dat, GIP de tek pat pan di rεguleshכn fכ di lipid mεtabolism, we de infכlכ di adiposyt difrεns εn lipid akyumyuleshכn.
Fig. 1. RETA ɔ SEMA tritmɛnt de ridyus di bɔdi wet ɛn i de mek di blɔd glukɔs we yu de fast fast.a Dɛn ripɔt pasɛnt chenj na di bɔdi wet frɔm di beslayn. b, Epididymal wayt adipose tisu weit bin kwantifay na di εndpכynt. c Fastin bכdi glukכs bin kwantifay na di beslayn εn tru di stכdi na indikεt tεm pכynt te di εndpכynt. d dεn ripot di tכmכro engraftmεnt כ 'tכmכr tek'.
GLP-1 risεptor: GLP-1 na intestinal L sεl dεm de sekret am εn i gεt bak glukכs-dipεndεnt insulinotropik ifekt, we de εnhans insulin sεntesis εn rilis, inhεbit glukagon sekreshכn, εn ridyus hεpatik glukכs autput. GLP-1 de delay bak di gastric ɛmti, i de mek yu satisfay, ɛn dat de mek yu nɔ it bɛtɛ it. i gεt protεktiv εn proliferativ ifekt pan pankrεas beta sεl dεm, we de εp fכ mεnten pankrεas fכ wok.
3. GC Risɛptɔ: .
afta i tay di GC rεsεpכta, glukagon de fכs akt pan di liva bay we i de protεkt glycogenolysis εn gluconeogenesis, we de εlevεt di bכdi glukכs lεvεl. insay lipid mεtabolism, i de protεkt lipolysis, we de inkrεs di rilis εn כksidεshכn fכ fεt asid fכ enεji. כnda nכmal fysiolojikal kכndishכn dεm, di glukכn sekreshכn de inhεbit we di blכd glukכs lεvεl de go כp fכ mεnten di glukכs bεlε.
(2) Advantej dɛn fɔ Tripul Agonist Akshɔn
as tripl agonist, GLP-3 kin aktibכt dεn tri rεsεpכta dεm ya wan tεm, we de εksyεrt sinagεstik ifekt dεm. bay we i de aktibכt GIP εn GLP-1 rεsεpכta dεm, i de εnhans glukכs-dipεndεnt insulin sekreshכn, mכr ifektiv wan lכs di blכd glukכs lεvεl. di inkrεs satiety εn dilay gastric εmpty we GLP-1 rεsεptכr aktibכshכn indyuz, wit di lipolysis we GC rεsεptכr aktibכshכn de promuot, kכlektivli kכntribyut to wet mεnejmεnt. dis mכlti-targeted mεkanism fכ akshכn de gi mכr kכmprεhεnsiv rεguleshכn fכ difrεn pathophysiological prכsεs dεm we de asai wit mεtabolik sik dεm.
Mekanism fכ akshכn fכ GLP-3 in mεtabolik sik dεm
mεtabolik sik dεm na wan klas כf kכndyushכn dεm we kin kכz fכ disrupshכn pan mεtabolik prכsεs dεm insay di bכdi, inklud kכmכn kכndyushכn dεm lεk mεtabolism, fכ fat, εn nכn-alkohol fεt liva sik. GLP-3 de du in ifekt pan dεn mεtabolik sik dεm ya tru in yכnik tripl agonist prכpati dεm.
(1) Mekanism fɔ Akshɔn pan Dayabitis
glukכs rεgulεshכn: GLP-3 de aktibכt GIP εn GLP-1 rεsεpכta dεm, we de εnhans glukכs-dipεndεnt insulin sekreshכn. we di glukכs lεvεl dεm na di bכdi go כp, i de mek di pankrεas beta sεl dεm mכr ifektiv fכ sekret insulin, we de mek di glukכs tek εn yuz am, we de mek di blכd glukכs lεvεl dכn. bay we i de inhibit glukagon sekreshכn εn ridyus di hεpatik glukכs autput, i de stεbyul di bכdi glukכs lεvεl mכr. Insay klinik trayal we involv pasɛnt dɛn wit tayp 2 mɛtabolism, GLP-3 tritmɛnt rizulta in signifyant ridyushɔn pan ɔl tu di fast ɛn postprandial blɔd glukɔs lɛvɛl.
di protεkshכn fכ di pankrεas beta sεl dεm: di aktibכshכn fכ di GLP-1 rεsεpכta nכ de nכmכ de protεkt insulin sekreshכn bכt i de protεkt εn proliferativ ifekt pan pankrεas beta sεl dεm. GLP-3 kin achy dis bay we i de kכntinyu fכ aktibכt di GLP-1 rεsεpכta, slo dכn beta sεl apoptosis, inkrεs dεn nכmba εn fכnshכn, we de impruv insulin sekreshכn kapasiti εn mεnten stebul bכdi glukכs lεvεl fכ lכng tεm.
(2) Di we aw pɔsin kin du sɔntin we pɔsin fat pasmak
rεgulεshכn fכ di εnεji we yu de it: GLP-3 de aktibכt di GLP-1 rεsεpכta dεm, i de delay di gεstrik εmpti, i de lכng di tεm we di it de rεtεn insay di bεlε, i de mek di it bכku bכku wan, εn i de ridyus di it we i de it. i kin akt pan di sεntri nεv sεstem fכ rεgεl di nyurotransmit dεm we de rilet to di apεtit, lεk fכ inhibit di rilis fכ כreksin, fכ ridyus di apεtit mכr, εn dat de kכntrכl di enεji we i de it.
inkrεs εnεji εkspεndishכn: aktibכshכn fכ di GC rεsεpכta de protεkt lipolysis, inkrεs di rilis εn כksidεshכn fכ fεt asid fכ enεji prodakshכn. di oksidashכn fכ fεt asid de gi εnεji to di bכdi, i de ridyus di fεt we i de stכr, εn i de εp fכ lכs di wet. aktibכshכn fכ di GIP rεsεpכta de tek pat bak pan εnεji mεtabolism rεguleshכn, we de inkrεs εnεji εkspεndishכn.
Figure 2 RETA tritmεnt de ridyus di bכdi wet εn adipositi, i de impruv di fastin bכdi glukכs. a Dɛn ripɔt pasɛnt chenj dɛn na di bɔdi wet frɔm di beslayn. b dεn wej di epididymal wayt adipos tisu na di εndpכynt εn nכmal to tכtal bכdi wet. c Fastin blɔd glukɔs bin kwantifay na di beslayn ɛn ɔlsay na di stɔdi na di tɛm pɔynt dɛn we dɛn sho te di ɛndpɔynt.
(3) Mεkanism fכ akshכn insay nכn-alkohol fεt liva sik
impruv di hεpatik lipid mεtabolism: GLP-3 de aktibכt di GC rεsεpכta, we de protεkt di brεk dכwn εn β-oksidashכn fכ fεt na di liva, we de ridyus fεt akyumyuleshכn na di liva. aktibכshכn fכ di GIP εn GLP-1 rεsεpכta dεm kin rεgεl di εksprεshכn fכ di jin dεm we riliyt to lipid mεtabolism insay di liva, upregulate di εksprεshכn fכ fεt asid transpכrta dεm εn fεt asid כksidayz dεm, we de mek fεt asid כptek εn כksidεshכn, εn fכ impruv di hεpatik lipid mεtabolism mכr.
εnhans insulin sεnsitiviti: pan כl we i de impruv glukכs rεguleshכn εn inkrεs insulin sekreshכn, GLP-3 kin εnhans hεpatik insulin sεnsitiviti bay we i de aktibכt GLP-1 rεsεpכta dεm. di εnhans insulin sεnsitiviti de εnhans di liva in rεspכns to insulin, bεtε inhεbit di hεpatik glukכs autput, ridyus di de novo fεt asid sεntesis, εn dat de mek di hεpatik stεatosis bεtε.
Aplikeshɔn ɛn Ifɛkt dɛn we GLP-3 gɛt pan Mɛtabolik sik dɛn
(1) Aw fɔ yuz am pan Dayabitis
lycemic Control Effects: GLP-3 de sho signifyant glycemic kontrכl ifekt dεm pan pasεnshכn dεm we gεt tayp 2 mεtabolism. Akɔdin to di data, di pasɛnt dɛn we dɛn trit wit GLP-3 sho se di ɛmoglobin A1c (HbA1c) lɛvɛl dɔn ridyus bad bad wan. Insay wan randomiz kɔntrol trayal we involv 353 pasɛnt dɛn wit tayp 2 mɛtabolism, di HbA1c lɛvɛl dɛn na di GLP-3 tritmɛnt grup bin dɛkɛd bay 1.64% frɔm di beslayn, we nɔ bin gɛt ɛni impɔtant chenj na di plesibo grup.
Kכmpεreshכn wit כda Drug dεm: We yu kכmpεr wit tradishכnal antidiabetic drog dεm lεk mεtfכmin כ GLP-1 rεsεptכr agonist, GLP-3 de sho se i gεt supεriכr bכdi glukכs kכntrכl ifekt dεm.
(2) Aplikeshɔn pan pɔsin we fat
Di ifɛkt dɛm we pɔsin kin gɛt we i de lɔs di wet: GLP-3 de sho se i gɛt bɔku wok fɔ trit pɔsin we fat pasmak. Insay klinik trayal dɛn we dɛn bin de tɔch big pipul dɛn we fat, dɛn bin si se dɛn dɔn lɔs bɔku bɔku wet afta 48 wiks we dɛn bin de trit dɛn wit difrɛn doz dɛn fɔ GLP-3. Insay wan trayal, di pasɛnt dɛn we dɛn trit wit 12mg doz fɔ GLP-3 bin gɛt avrej wet lɔs we na 24.2% afta 48 wik, we yu kɔmpia am wit 2.1% nɔmɔ na di plesibo grup. Apat frɔm dat, 83% pan di patisipan dɛn na di ay-dos grup bin ajɔst di wet lɔs we na 15% ɔ mɔ, we pas di 2% rit na di plasɛbo grup fa fawe.
Lכng Tεm Efεkt: GLP-3 de mεnten di weit lכs ifekt dεm fayn fayn wan tru di tritmεnt tεm. Dis sho se if yu yuz am fɔ lɔng tɛm, dat kin ɛp fɔ mek yu gɛt stebul wet ɛn mek yu nɔ gɛt bɔku bɔku wet bak, we go bɛnifit fɔ mek yu ebul fɔ mɛn yu fat fɔ lɔng tɛm.
(3) Aplikeshɔn insay nɔ-alkohol fat liva sik
Liva fεt rεdukshכn: Insay pasεnshכn dεm we gεt mεtabolik disfכnkshכn-asכsiet fεt liva sik εn liva fεt kכntεnt ≥10%, GLP-3 tritmεnt rεsult in signifyant rεdukshכn pan liva fεt kכntεnt. Insay wan randomized, double-blind, placebo-controlled trial, na 24 wik, liva fat kɔntinyu fɔ go dɔŋ bay 81.4% ɛn 82.4% frɔm di beslayn insay di 8 mg ɛn 12 mg doz grup, rispɛktvɔli, we di plasɛbo grup inkri bay 0.3% nɔmɔ.
Advantej ɛn Potensial fɔ di Tripul Agonist
GLP-3 kכmprεhεnsivli rεgεl mכltipכl patכfysiolojikal path dεm fכ mεtabolik sik dεm bay we i de aktibכt GIP, GLP-1, εn GC rεsεpכta dεm wan tεm. frכm bכdi glukכs kכntrכl, wet mεnejmεnt, to impruv hεpatik lipid mεtabolism, dis mכlti-target mεkanism fכ akshכn tiorikal wan de כfr mכr kכmprεhεnsiv kכrekshכn fכ mεtabolik dizכrd dεm kכmpεr to singl-tכgεt drog dεm, we de sho pכtεnshal fכ adrεs di kכmpleks etioloji fכ mεtabolik sik dεm. Di klinik trial data we de naw sho se GLP-3 dɔn ajɔst impɔtant ifɛkt dɛn pan di tritmɛnt fɔ mɛtabolik sik dɛn lɛk mɛtabolism, fat, ɛn nɔ-alkohol fat liva sik.
Dɔn
as nכvel tripl agonist, GLP-3 de hol prכmis fכ di tritmεnt fכ mεtabolik sik dεm.
Sos dɛn we dɛn pul
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Prodak we de fɔ yuz fɔ risach nɔmɔ:
