Na Cocer Peptides 
hashize iminsi 18
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBURANISHA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemewe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Incamake ya Triple Agonist
Mu myaka yashize, hamwe n’ubushakashatsi bwimbitse ku ndwara ziterwa na metabolike, iterambere ry’imiti myinshi ya agonist yibasira imisemburo myinshi ya hormone yabaye ingingo ishyushye. GLP-3 ni agoniste inshuro eshatu agonist ya glucose iterwa na insulineotropique polypeptide (GIP), glucagon imeze nka peptide-1 (GLP-1), hamwe na reseptor ya glucagon (GC).
(1) Ishingiro ryimiterere yimikorere ya Hormone
GIP Receptor: GIP ni imisemburo yo mu nda ya insuline isohora imisemburo isohoka na selile K mu mara mato, irekurwa vuba nyuma yo kurya. Iyo GIP ihujwe na reseptor ya GIP, GIP itera ururenda rwa insuline, kandi izi ngaruka zikangura ziterwa na glucose, bivuze ko uko glucose yamaraso izamuka, GIP yongera imbaraga zayo zo gusohora insuline, ifasha kugumana urugero rwa glucose rwamaraso. Byongeye kandi, GIP igira uruhare mugutunganya metabolisme ya lipide, bigira uruhare mu gutandukanya adipocyte no kwirundanya kwa lipide.
Igishushanyo 1. Ubuvuzi bwa RETA cyangwa SEMA bugabanya uburemere bwumubiri kandi butezimbere glucose yamaraso yo kwiyiriza ubusa. b, Epididymal yera adipose yuburemere bwa tissue yagereranijwe kumpera. c Kwiyiriza amaraso glucose byapimwe kuri baseline kandi mubushakashatsi bwakozwe mugihe cyerekanwe kugeza imperuka. d Kumenyekanisha ibibyimba cyangwa 'kubyimba gufata ' biravugwa.
GLP-1 reseptor: GLP-1 isohorwa na selile zo munda L kandi ikagira n'ingaruka ya glucose iterwa na insuline ya insuline, kongera insuline ya insuline no kurekura, kubuza gusohora glucagon, no kugabanya glucose ya hepatike. GLP-1 nayo itinda gusiba gastric, ikongera guhaga, bityo bikagabanya gufata ibiryo. Ifite ingaruka zo gukingira no gukwirakwira kuri selile beta pancreatic beta, ifasha kugumana imikorere ya pancreatic.
3. GC yakira:
Nyuma yo guhambira reseptor ya GC, glucagon ikora cyane cyane mwumwijima itera glycogenolysis na gluconeogenez, bityo bikazamura urugero rwa glucose yamaraso. Muri metabolism ya lipide, itera lipolysis, ikongera irekura na okiside ya aside irike yingufu. Mubihe bisanzwe byimiterere yumubiri, glucagon isohoka irahagarikwa mugihe glucose yamaraso izamutse kugirango glucose ibungabunge.
(2) Ibyiza bya Triple Agonist Igikorwa
Nka triple agonist, GLP-3 irashobora gukora icyarimwe gukora reseptors eshatu, bikagira ingaruka zingirakamaro. Mugukoresha reseptor ya GIP na GLP-1, byongera imisemburo ya glucose iterwa na glucose, bikagabanya cyane glucose yamaraso. Kwiyongera guhaga no gutinda gusiba gastrica iterwa no gukora GLP-1 yakira reseptor, hamwe na lipolysis yatejwe imbere no gukora GC reseptor, hamwe bigira uruhare mugucunga ibiro. Ubu buryo bugamije ibikorwa byinshi butanga amabwiriza arambuye yuburyo butandukanye bwa patrophysiologique bujyanye nindwara ziterwa na metabolike.
Uburyo bwibikorwa bya GLP-3 mu ndwara za metabolike
Indwara ziterwa na metabolike nicyiciro cyimiterere iterwa nihungabana ryimikorere ya metabolike mumubiri, harimo nibisanzwe nka metabolism, umubyibuho ukabije, nindwara zumwijima zidafite inzoga. GLP-3 igira ingaruka kuri ziriya ndwara ziterwa na metabolike yihariye ya triple agonist yihariye.
(1) Uburyo bwibikorwa muri Diyabete
Amabwiriza ya Glucose: GLP-3 ikora reseptor ya GIP na GLP-1, ikongerera glucose iterwa na glucose. Iyo glucose yamaraso izamutse, itera neza cyane ingirabuzimafatizo ya beta yo gusohora insuline, igatera glucose no kuyikoresha, bityo bikagabanya urugero rwa glucose. Muguhagarika imisemburo ya glucagon no kugabanya umusaruro wa glucose ya hepatike, irusheho gutuma urugero rwa glucose rwamaraso. Mu bigeragezo bivura abarwayi bafite metabolism yo mu bwoko bwa 2, kuvura GLP-3 byatumye igabanuka rikabije haba mu kwiyiriza ubusa no mu maraso glucose nyuma yo kubyara.
Kurinda uturemangingo twa beta pancreatic: Gukora reseptor ya GLP-1 ntabwo bitera gusohora insuline gusa ahubwo binagira ingaruka zo gukingira no gukwirakwira kuri selile beta. GLP-3 irashobora kubigeraho mugukomeza gukora reseptor ya GLP-1, kugabanya umuvuduko wa beta selile apoptose, kongera umubare wimikorere, bityo bikongerera ubushobozi bwo gusohora insuline no gukomeza glucose yamaraso mu gihe kirekire.
(2) Uburyo bwibikorwa mubyibushye
Kugena gufata ingufu: GLP-3 ikora reseptor ya GLP-1, gutinda gusiba gastrica, kongera igihe cyo kugaburira ibiryo mu gifu, kongera guhaga, no kugabanya ibiryo. Irashobora gukora kuri sisitemu yo hagati yo kugenzura ibyokurya bifitanye isano no kurya, nko kubuza irekurwa rya orexine, bikagabanya ubushake bwo kurya, bityo bikagenzura gufata ingufu.
Kongera ingufu zikoreshwa: Gukoresha reseptor ya GC biteza lipolysis, kongera irekurwa na okiside ya aside irike kugirango itange ingufu. Okiside ya aside irike itanga imbaraga mumubiri, igabanya ububiko bwamavuta, kandi igafasha kugabanya ibiro. Gukora reseptor ya GIP bigira uruhare no kugenzura ingufu za metabolism, kongera ingufu zikoreshwa.
Igicapo 2 Kuvura RETA bigabanya uburemere bwumubiri nubwitonzi, butezimbere glucose yamaraso. impinduka ku ijana muburemere bwumubiri uhereye kubanze byavuzwe. b Epididymal tissue adipose tissue yapimwaga kumpera yanyuma kandi isanzwe muburemere bwumubiri. c Kwiyiriza amaraso glucose byapimwe kuri baseline kandi mubushakashatsi bwakozwe mugihe cyerekanwe kugeza imperuka.
(3) Uburyo bwibikorwa mu ndwara zumwijima zidafite inzoga
Kunoza metabolisme ya hepatike: GLP-3 ikora reseptor ya GC, igatera gusenyuka no β-okiside yibinure mu mwijima, bityo bikagabanya kwegeranya amavuta mu mwijima. Gukora kwakirwa kwa GIP na GLP-1 birashobora kugenga imiterere ya genes zijyanye na metabolisme ya lipide mu mwijima, bikagenga imvugo yabatwara aside irike hamwe na okiside ya aside irike, bityo bigatuma aside irike ifata hamwe na okiside, kandi bikarushaho kunoza metabolisme ya hepatike.
Kongera imbaraga za insuline: Nubwo kunoza amabwiriza ya glucose no kongera imisemburo ya insuline, GLP-3 irashobora kongera insuline ya insuline ikoresheje reseptor ya GLP-1. Kongera imbaraga za insuline byongera umwijima kwitabira insuline, bikarinda neza umusaruro wa glucose hepatike, kugabanya synthesis ya de novo fatty acide, bityo bikagabanya indwara ya hepatike.
Porogaramu n'ingaruka za GLP-3 mu ndwara za metabolike
(1) Porogaramu muri Diyabete
Ingaruka zo kugenzura lycemic: GLP-3 yerekana ingaruka zikomeye zo kurwanya glycemic kubarwayi bafite metabolism yo mu bwoko bwa 2. Dukurikije imibare, abarwayi bavuwe na GLP-3 bagaragaje igabanuka rikabije rya hemoglobine A1c (HbA1c). Mu igeragezwa ryateganijwe ryitabiriwe n’abarwayi 353 bafite metabolism yo mu bwoko bwa 2, urwego rwa HbA1c mu itsinda ry’ubuvuzi rya GLP-3 rwaragabanutseho 1,64% bivuye ku murongo fatizo, mu gihe nta mpinduka nini yagaragaye mu itsinda rya placebo.
Ugereranije n’ibindi biyobyabwenge: Ugereranije n’imiti gakondo ya antidiabete nka metformin cyangwa GLP-1 reseptor agonist, GLP-3 yerekana ingaruka nziza zo kugenzura amaraso glucose.
(2) Gukoresha umubyibuho ukabije
Ingaruka zo kugabanya ibiro: GLP-3 yerekana akamaro gakomeye mukuvura umubyibuho ukabije. Mu bigeragezo bivura byibasiye abarwayi bafite umubyibuho ukabije, kugabanuka gukabije byagaragaye nyuma y'ibyumweru 48 bivurwa hamwe na dosiye zitandukanye za GLP-3. Mu igeragezwa rimwe, abarwayi bavuwe hamwe na 12mg ya GLP-3 bagabanutse ibiro 24.2% nyuma yibyumweru 48, ugereranije na 2,1% gusa mumatsinda ya placebo. Byongeye kandi, 83% byabitabiriye itsinda ryinshi-ryinshi ryagabanutse ibiro 15% cyangwa birenga, birenze kure igipimo cya 2% mumatsinda yabobo.
Ingaruka z'igihe kirekire: GLP-3 ikomeza ingaruka zo kugabanya ibiro neza mugihe cyo kuvura. Ibi birerekana ko gukoresha igihe kirekire bishobora gufasha kugumana ibiro bitajegajega no kwirinda kongera ibiro, bifasha mugucunga igihe kirekire kubyibushye.
(3) Gushyira mu bikorwa indwara zumwijima zidafite inzoga
Kugabanya ibinure byumwijima: Ku barwayi bafite metabolike idakora neza ifitanye isano n’amavuta y’umwijima hamwe n’ibinure by’umwijima ≥10%, kuvura GLP-3 byatumye igabanuka ryinshi ry’amavuta y’umwijima. Mu igeragezwa ryateganijwe, rihumye-rihumye, rigenzurwa na platbo, mu byumweru 24, ibinure byumwijima byagabanutseho 81.4% na 82.4% bivuye kuri baseline mu matsinda ya mg 8 na mg 12, mugihe itsinda rya placebo ryiyongereyeho 0.3% gusa.
Ibyiza nubushobozi bwa Triple Agonist
GLP-3 igenga byimazeyo inzira nyinshi za patrophysiologique yindwara ziterwa na metabolike icyarimwe ikora GIP, GLP-1, na GC. Kuva mu kugenzura amaraso glucose, gucunga ibiro, kugeza kunoza metabolisme ya hepatike, ubu buryo bugamije ibikorwa byinshi butanga uburyo bunoze bwo gukosora indwara ziterwa na metabolike ugereranije n’imiti imwe, yerekana ubushobozi bwo gukemura ibibazo by’indwara ziterwa na metabolike. Ibizamini byo kwa muganga biriho byerekana ko GLP-3 imaze kugera ku ngaruka zikomeye mu kuvura indwara ziterwa na metabolisme nka metabolism, umubyibuho ukabije, n'indwara y'umwijima idafite inzoga.
Umwanzuro
Nkibintu bitatu byitwa agonist, GLP-3 ifite amasezerano yo kuvura indwara ziterwa na metabolike.
Inkomoko
[1] Allard C, Cota D, Quarta C. Imiti ya Poly-Agonist Pharmacotherapies yindwara ya Metabolic: Ibyiringiro nibibazo bishya [J]. Ibiyobyabwenge, 2024,84 (2): 127-148.DOI: 10.1007 / s40265-023-01982-6.
[2] Kaur M, Misra S. Isubiramo ryibiyobyabwenge byiperereza GLP-3, igitabo gishya cyitwa agonist agent cyo kuvura umubyibuho ukabije [J]. Ikinyamakuru cyo mu Burayi cya Pharmacology Clinical, 2024,80 (5): 669-676.DOI: 10.1007 / s00228-024-03646-0.
[3] Lopez DC, Pajimna JT, Milan MD, n'abandi. 7792 Ingaruka za GLP-3 zo kugabanya ibiro ningaruka za Cardiometabolike mu bantu bakuru: Isubiramo rifatika hamwe na Meta-Isesengura [J]. Ikinyamakuru cya Sosiyete Endocrine, 2024,8 (Umugereka_1): bvae163-bvae749.DOI: 10.1210 / jendso / bvae163.749.
[4] Jastreboff AM, Kaplan LM, Frías JP, n'abandi. Inshuro eshatu-Hormone-yakira Agonist GLP-3 kubyibushye - Ikigeragezo Cyicyiciro cya 2 [J]. Ikinyamakuru gishya cy’ubuvuzi cy’Ubwongereza, 2023.389 (6): 514-526.DOI: 10.1056 / NEJMoa2301972.
[5] Doggrell S A. Ese GLP-3 (LY3437943), GLP-1, GIP, na glucagon reseptor agonist intambwe yatewe mukuvura metabolism n'umubyibuho ukabije? [J]. Igitekerezo cyinzobere ku biyobyabwenge byiperereza, 2023.32 (5): 355-359.DOI: 10.1080 / 13543784.2023.2206560.
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