▎ GLP-2 Risach
Wetin na di risach bakgrɔn fɔ GLP-2?
di divεlכpmεnt fכ GLP-2, we na sεntetik polipεptida dכg, kכmכt frכm we dεn no di limitεshכn dεm fכ GLP-1 rεsεptכr agonist dεm fכ trit tayp 2 mεtabolism εn fכ fat. pan ɔl we di GLP-1 rεsεptכr agonist dεm de εksεl in bכdi glukכs kכntrכl εn weit lכs, sayɛnsman dεm fכnshכn se dεn wik aktibכshכn fכ GIP rεsεptכr dεm de limited tεrapi ifekt dεm. So, risach tim dεm bin aim fכ divεlכp nכvel drog dεm we ebul fכ aktibכt כl tu di GIPR εn GLP-1R fכ mכr kכmprεhεnsiv glycemic kכntrכl εn wet mεnejmεnt [1]..
Dɛn bin du bɔku prɛklinik ɛn klinik trayal dɛn we dɛn bin de du di divɛlɔpmɛnt.
Prεklinik animal stεdi dεm evaluate fכmakodaynamik prכpati dεm, kכnfכm in pכtεnshal in glycemic kכntrכl εn weit lכs. Faz I klinik trial dεm bin fכs ases sef, tכlerabiliti, εn fכmakokinetiks, we sho gud sef
ɛn we pɔsin kin ebul fɔ bia wit am. Faz II trayal dεm fכs εksplכr efikכs εn sef pan difrεnt dכz dεm in tayp 2 mεtabolism pasεnshכn dεm, fכs dεtermine ifektiv doz rεnj dεm. Pivotal Faz III trayal dεm lεk di SURPASS siriכs, we involv big kכhכt dεm fכ tayp 2 mεtabolism pasεnshכn dεm, sho se GLP-2 sכmtεm autpכfכm εgzistin GLP-1 rεsεptכr agonist dεm fכ lכs blכd glukכs εn wet, we gi robust pruf fכ makεt aplikεshכn [1]..
i kכmכp fכ 39 amino asid dεm wit strכkchכral modifyushכn fכ εnhans stεbiliti εn efikכs, in yכnik strכkchכ de intagret di akshכn dεm fכ GIP εn GLP-1 insay wan mכlikul, we de aktibכt כmon rεsεpכta dεm we involv insay glycemic kכntrכl tru tu mεkanism dεm.
na wan say, i de wok pan di pankrias fכ mek insulin sekreshכn εn fכ mek di glukכn kכmכt fכ ridyus di glukכs na di bכdi; na di כda say, i de wok pan di sεntri nεv sεstem fכ delay di gεstrik εmpti, inkrεs fכ sati, εn rεdכks fכ it εn it fכ mεnejmεnt di wet. dis tu mεkanism de gi GLP-2 yunik advantej fכ trit tayp 2 mεtabolism εn fכ fat, we de gi di sik pipul dεm mכr kכmprεhεnsiv tεrapi opshכn dεm [1]..
Wetin na di mεkanism fכ akshכn fכ GLP-2?
GLP-2 de lכs di glukכs na di bכdi tru mכltipכl mεkanism dεm:
aktibכshכn fכ GLP-1 rεsεpכta dεm: i de biεn GLP-1 rεsεpכta dεm pan pankrεas β sεl dεm, i de mεkכl nεchכral GLP-1 fכ protεkt insulin sεntesis, sekreshכn, εn glukכs sεns we i de ridyus glukכn sekreshכn fכ εnhans satiety εn sכpres apεtit. insay tayp 2 mεtabolism pasεnshכn dεm, we dεn aktibכt GLP-1 rεsεpכta dεm de inkrεs insulin sekreshכn fכ impruv glycemic kכntrכl, we fכ inhεbit glukכn rilis de ridyus di bכdi glukכs sכs dεm mכr, we de εp glycemic rεguleshכn [2]..
aktibכshכn fכ GIP rεsεptor dεm: we i de akt pan GIP rεsεpכta dεm, aktibכshכn de εnhans insulin sεnsitiviti εn sekreshכn. di GIP risεptor dεm de mεnli insay tisu dεm lεk pankrεas β sεl dεm, εn aktibכshכn tru intasεlulyar signal path dεm de inkrεs insulin sekreshכn εn impruv sεl rεspכns to insulin fכ mכr ifektiv bכdi glukכs rεdukshכn [2] . dis dual risεptor agonism de mek GLP-2 mכr ifektiv fכ protεkt insulin sekreshכn εn inhεbit glukagon rilis pas singl GLP-1 rεsεpכta agonist dεm [2]. .
Dilayed Gastric Emptying and Increased Satiety: I de delay gastric emptying, i de mek di it de rεtεn di bεlε fכ lכng fכ slo di nyutriεnt absכpshכn εn avכyd di bכdi glukכs spik afta i it. pan tap dat, we yu akt pan di sεntri nεv sεstem fכ inkrεs di satiety de rεdכks di apεtit εn di it we yu de it, patikyuכl bεnεfit fכ fat we kin kכmכt wit tayp 2 mεtabolism, we de εp fכ impruv insulin rεsistεns εn כvala mεtabolik stetכs [3]..
Impruv Insulin Sεnsitiviti εn Lipid Dayabitis: fכ εlevεt di adiponectin lεvεl—wan fεt sεl fכktכ we riliyt to insulin sεnsitiviti—de εp fכ impruv insulin sεnsitiviti, we de mek sεl dεm ebul fכ tek εn yuz glukכs mכr efyushכn fכ ridyus glukכs na di bכdi [2] (Anonymous, 2023). i de impruv di lipid profayl dεm bak, wit pכtεnshal prכtektiv ifekt dεm pan di kכdivaskyul hεlth, dεn sho se i de impruv bכdi prεshכn εn rεdכks LDL kכlestכl εn triglisεrayd [3]..
Wetin na di stɔdi dɛn we gɛt fɔ du wit dis?
GLP-2 de sho se i de du sכmtin we i de du fכ mεnεj di wet fכ di wan dεm we fat εn di tayp 2 mεtabolism pasεnshכn dεm. Insay di SURMOUNT-2 stɔdi, wan Faz 3, dabl-blaynd, randomiz, plasɛbo-kɔntrol trial we dɛn du na sɛvin kɔntri, big pipul dɛn we ol ≥18 ia wit BMI ≥27 kg/m² ɛn HbA1c 7–10% bin randomiz fɔ gɛt wik sabkyutan GLP-2 (10 mg ɔ 15 mg) ɔ plasɛbo fɔ 72 wik. Bay wik 72, di weit lɔs pasɛnt na bin −12.8% ɛn −14.7% insay di GLP-2 10 mg ɛn 15 mg grup dɛn versus −3.2% insay di plasɛbo grup, wit ɛstimat tritmɛnt difrɛns we na −9.6 ɛn −11.6 pasɛnt poɛnt kɔmpia to plasɛbo (p < 0.0001). Apat frɔm dat, mɔ GLP-2-trit pasɛnt dɛn ajɔst ≥5% weit lɔs (79–83% vs. 32%) (Garvey WT, 2023). Wit beslayn min wet 100.7 kg, BMI 36.1 kg/m², ɛn HbA1c 8.02%, 72 wik tritmɛnt wit GLP-2 nɔ jɔs ridyus di wet bɔku bɔku wan bɔt i impɔtant bak fɔ mek di glycemic kɔntrol [4]. .
fכ impruv mεtabolism-rεlatεd nyuropathy, risεch sho se GLP1-RA dεm kin ridyus dimεnshכn risk insay tayp 2 mεtabolism pasεnshכn bay we dεn de impruv mεmכri, lanin, εn כvakom di kכgnitiv impεryans. As dual GIP-RA/GLP-1RA, GLP-2 bin stכdi in nyuroblastoma sel layn (SHSY5Y) fכ in ifekt pan nyuronal growth (CREB εn BDNF), apoptosis (BAX/Bcl2 rεshכ), difrεns (pAkt, MAP2, GAP43, εn AGBL4), εn insulin rεsistεns (GLUT1, GLUT4, GLUT3, εn SORBS1) mak dɛn. i fכnshכn se i de εksyεrt nyuroprotεktiv ifekt dεm bay we i de aktibכt di pAkt/CREB/BDNF path εn dכwnstrim signal kaskad, we de kכntrכl haypa glycemia- εn insulin rεsistεns-rεlatεd ifekt dεm na di nyuronal lεvεl. so, GLP-2 kin impruv di nyurodijεnεreshכn we di haypa glycemia indyuz εn i kin כvakom nyuronal insulin rεsistεns, we de gi nyu insayt fכ mεnεj mεtabolism-rεlatεd nyuropathy [5]..
insay tayp 2 mεtabolism tritmεnt advansmεnt, GLP-2, wan nכvel haypoglycemic drog, bi di fכs aprכv dual GIP/GLP-1R agonist fכ mεtabolism na di US Mכltipכl big klinik trial dεm kכnfכm in signifyant glycemic-lowering εn weight-loss ifekt dεm, wit pכtεnshal fכ kכdivaskyul protεkshכn. di kכnsεpt fכ sεntetik pεpti dεm dεn opin plεnti posisibilti dεm we dεn nכ εksplכr fכ GLP-2. Trial ɛn pruf dɛm we de go bifo sho se na prɔmis drɔg fɔ non-alcoholic fatty liver disease (NAFLD), rεnal protεkshɔn, ɛn nyuroprotεkshɔn [6]..
Fɔ tɔk bɔt di lɔng tɛm ifɛkt pan di at ɛn di blɔd wɛlbɔdi, GLP-2 kin ridyus di risk fɔ di at ɛn di blɔd sik (CVD) bay we i de mek pɔsin lɔs di wet. Wan stכdi we de egzamin GLP-2 in impak pan fat εn CVD ivin dεm pan US big pipul dεm fכnshכn se pan dεn wan dεm we fit fכ GLP-2 tritmεnt, dεn εstimat 15 mg tεrapi fכ achy ≥15% εn ≥20% weit lכs insay 70.6% εn 56.7% pan big pipul dεm, rispεktivli, we translet to 58.8% rεdukshכn pan fat prεvalεns. pan pipul dεm we nכ gεt CVD, di εstimat 10 ia CVD risk dכn dכn frכm 10.1% 'pri-tritmεnt' to 7.7% 'post-tritmεnt,' we riprizent absכlut risk rεdukshכn fכ 2.4% εn rilitiv risk rεdukshכn fכ 23.6%, we pכtεnshal fכ prεvεnt 2 miliכn CVD ivin dεm [7].
Dɔn
in sכmari, GLP-2 na nכvel dual agonist fכ GIP εn GLP-1 rεsεpכta dεm, we de hכl sכm imכpכtants fכ trit tayp 2 mεtabolism εn fכ fat. i de mכr ifektiv fכ protεkt insulin sekreshכn, inhεbit glukagon rilis, εn prεsisli rεgεl bכdi glukכs, ridyus komplikashכn risk dεm we i de impruv pankrεas β-sεl fכnshכn εn delay mεtabolism prכgreshכn, wit kכdiprotεktiv ifekt dεm. Insay tritmɛnt fɔ fat, i de ridyus di it we pɔsin de it fayn fayn wan, i de stɔp di apɛtit, i de mek pɔsin satis, i de ɛp fɔ lɛ pɔsin nɔ gɛt bɔku bɔku wet, ɛn i de mek di prɔblɛm dɛn we kin apin we pɔsin fat pasmak, ɛn i kin mek di insulin nɔ de wok fayn ɛn di lipid mɛtabolism bɛtɛ. Apat frɔm dat, i de sho se i kin ebul fɔ trit mɛtabolik dizayd lɛk nɔ-alkoholik stiatohepatitis, slip apnia sindrom, ɛn at fayl, we de gi kɔmprɛhɛnsif tritmɛnt bay we i de ɛp fɔ mek bɔku mɛtabolik paramita dɛn bɛtɛ. Di injɛkshɔn schedule we i gɛt wan tɛm insay di wik de mek i izi fɔ du ɛn di pɔsin we sik de fala di lɔ. We GLP-2 de kɔntrol di glukɔs ɛn wet na di blɔd fayn fayn wan, ridyus di prɔblɛm dɛn we kin apin to pɔsin, ɛn i kin mek dɛn bɔdi kɔndishɔn, di tin dɛn we dɛn kin du ɛvride, ɛn di kwaliti fɔ layf bɛtɛ bɛtɛ wan, i kin mek di sikman dɛn gɛt kɔnfidɛns pan di we aw dɛn de mɛn di sik, i kin mek dɛn nɔ gɛt bɔku prɔblɛm dɛn we dɛn kin gɛt na dɛn maynd, ɛn i kin mek dɛn ebul fɔ adap to pipul dɛn na di soshal layf.
Bɔt di pɔsin we rayt di buk
Di tin dɛm we wi dɔn tɔk bɔt, na ɔl di tin dɛm we Cocer Peptides dɔn du risach, ɛdit ɛn kɔmpilayt.
Sayɛns Jɔnal Author
Dɔktɔ Wiliam T. Gavi na wan big masta sabi bukman ɛn risachman we gɛt fɔ du wit bɔku bɔku big big institiushɔn dɛn, lɛk di Yunivasiti ɔf Alabama na Bɛmingham, Aston Yunivasiti, ɛn di Bɛmingham Veterans Afɛj Mɛdikal Sɛnta. In akademik bakgrɔn ɛn in wok ɛkspiriɛns span bɔku difrɛn disiplin dɛn insay di mɛdikal ɛn sayɛns fild dɛn. Dɔktɔ Garvey dɔn mek bɔku kɔntribyushɔn to di fil dɛm fɔ ɛndokrinɔlɔji ɛn mɛtabolism, nyutrishɔn ɛn itɛttiks, bayɔkemistri ɛn mɔlikul bayoloji, ɛn bak jenɛral ɛn intanɛnt mɛrɛsin, wit patikyula fɔs pan di kadiovaskular sistɛm ɛn kadiɔlɔji. Bɔku pipul dɛn dɔn no ɛn ɔnɔ in wok, mɔ we dɛn kɔl am Highly Cited Researcher in di Cross-Field kategori fɔ ɔl tu di 2023 ɛn 2024, we sho di big impak ɛn inflɛns we in risach gɛt pan di brayt sayɛns kɔmyuniti.
Dכkta Garvey in risach intres εn εkspεriεns de go to difrεn aspek dεm fכ mεtabolik sik dεm εn dεn mεnejmεnt. I dɔn de wok tranga wan fɔ stɔdi di mɛtabolism mɛlit, fɔ fat, ɛn di kɔmplikeshɔn dɛn we gɛt fɔ du wit dɛn, we i aim fɔ fɛn nyu tritmɛnt strateji ɛn fɔ mek di pɔsin in autkam bɛtɛ. In wok inkɔmpas besik sayɛns risach, klinik trial, ɛn transleshɔnal stɔdi, we de briŋ di gap bitwin di tin dɛn we dɛn dɔn fɛn na lɛbɔretri ɛn di rial wɔl mɛdikal aplikeshɔn dɛn. Tru in bɔku risach, Dɔkta Garvey dɔn kɔntribyut fɔ ɔndastand mɔ bɔt di ɔndalayn mɛkanism dɛm fɔ mɛtabolik disɔda ɛn i dɔn ɛp fɔ shep klinik gaydlayn ɛn tritmɛnt protɔkɔl dɛm na di fild fɔ ɛndokrinɔlɔji ɛn mɛtabolism. Dɛn rayt Dɔktɔ Wiliam T. Gavi insay di rɛfrɛns fɔ saytayshɔn [4].
