Na Cocer Peptides 
hashize iminsi 18
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA 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 byemejwe 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 gutera indwara ziterwa na metabolike, iterambere ry’imiti myinshi ya agoniste yibasira imisemburo myinshi ya hormone yabaye ingingo ishyushye. Retatrutid ni agoniste inshuro eshatu agonist ya glucose iterwa na insulineotropique polypeptide (GIP), glucagon isa na 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 cya 1. Ubuvuzi bwa RETA cyangwa SEMA bugabanya uburemere bwumubiri kandi butezimbere glucose yamaraso. 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 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 tronc agonist, Retatrutid irashobora gukora icyarimwe gukora reseptors eshatu, ikagira ingaruka zoguhuza. 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 na GC yakira 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 Retatrutid mu ndwara za metabolike
Indwara ziterwa na metabolike nicyiciro cyimiterere iterwa nihungabana ryimikorere ya metabolike mumubiri, harimo nibisanzwe nka diyabete, umubyibuho ukabije, nindwara zumwijima zidafite inzoga. Retatrutid igira ingaruka kuri izi ndwara ziterwa na metabolike binyuze mumiterere yihariye ya agonist.
(1) Uburyo bwibikorwa muri Diyabete
Amabwiriza ya Glucose: Retatrutid ikora reseptor ya GIP na GLP-1, ikongerera glucose iterwa na insuline. Iyo glucose yamaraso izamutse, itera neza cyane ingirabuzimafatizo ya beta ya pansreatic beta 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 by’amavuriro birimo abarwayi ba diyabete yo mu bwoko bwa 2, kuvura Retatrutid byatumye igabanuka rikabije haba mu kwiyiriza ubusa no mu maraso glucose nyuma yo kubyara.
Kurinda uturemangingo twa beta pancreatic beta: Gukora reseptor ya GLP-1 ntabwo bitera gusohora insuline gusa ahubwo binagira ingaruka zo gukingira no gukwirakwira kuri selile beta. Retatrutid 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 mumaraso mugihe kirekire.
(2) Uburyo bwibikorwa mubyibushye
Kugenga gufata ingufu: Retatrutid 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 yapimwe 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: Retatrutid ikora reseptor ya GC, igatera gusenyuka no β-okiside yibinure mu mwijima, bityo bikagabanya kwirundanya kw'umwijima mu mwijima. Gukora kwakirwa kwa GIP na GLP-1 birashobora kugenga imvugo ya genes zijyanye na metabolisme ya lipide mu mwijima, igenga imiterere yabatwara aside irike hamwe na okiside ya aside irike, bityo bigatuma aside irike ifata na okiside, kandi bikarushaho kunoza metabolisme ya lipide.
Kongera imbaraga za insuline: Mugihe kunoza amabwiriza ya glucose no kongera imisemburo ya insuline, Retatrutid irashobora kongera insuline ya insuline ikoresheje reseptor ya GLP-1. Kongera imbaraga za insuline byongera umwijima kwitabira insuline, bikarinda neza umusaruro wa glucose ya hepatike, kugabanya synthesis ya de novo fatty acide, bityo bikagabanya indwara ya hepatike.
Porogaramu n'ingaruka za Retatrutid mu ndwara za metabolike
(1) Porogaramu muri Diyabete
Ingaruka zo Kurwanya lycemic: Retatrutid yerekana ingaruka zikomeye zo kurwanya glycemic kubarwayi barwaye diyabete yo mu bwoko bwa 2. Dukurikije imibare, abarwayi bavuwe na Retatrutid bagaragaje igabanuka rikabije rya hemoglobine A1c (HbA1c). Mu igeragezwa ryateguwe ryitabiriwe n’abarwayi 353 barwaye diyabete yo mu bwoko bwa 2, urwego rwa HbA1c mu itsinda ry’ubuvuzi bwa Retatrutid rwagabanutseho 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, Retatrutid yerekana ingaruka nziza zo kurwanya glucose yamaraso.
(2) Gukoresha umubyibuho ukabije
Ingaruka zo kugabanya ibiro: Retatrutid yerekana akamaro gakomeye mukuvura umubyibuho ukabije. Mu bigeragezo by’amavuriro byibasira abarwayi bafite umubyibuho ukabije, kugabanuka gukabije byagaragaye nyuma yibyumweru 48 bivurwa hamwe na dosiye zitandukanye za Retatrutid. Mu igeragezwa rimwe, abarwayi bavuwe bafite 12mg ya Retatrutid bagabanutseho ibiro 24.2% nyuma yibyumweru 48, ugereranije na 2,1% gusa mumatsinda yabobo. Byongeye kandi, 83% byabitabiriye itsinda ryinshi-ryinshi ryagabanutse ibiro 15% cyangwa birenga, birenze kure igipimo cya 2% mumatsinda yabobo.
Ingaruka z'igihe kirekire: Retatrutid ikomeza ingaruka zo kugabanya ibiro mugihe cyo kuvura. Ibi birerekana ko gukoresha igihe kirekire bishobora gufasha kugumana ibiro bihamye no kwirinda kugarura ibiro, bifitiye akamaro gucunga igihe kirekire umubyibuho ukabije.
(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 Retatrutid 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 ku murongo fatizo mu matsinda 8 ya mg na mg 12, mu gihe itsinda rya placebo ryiyongereyeho 0.3% gusa.
Ibyiza nubushobozi bwa Triple Agonist
Retatrutid igenga byimazeyo inzira nyinshi za pathophysiologique 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 igamije intego imwe, byerekana ubushobozi bwo gukemura ibibazo bya etiologiya y’indwara ziterwa na metabolike. Ibizamini byo kwa muganga biriho byerekana ko Retatrutid imaze kugera ku ngaruka zikomeye mu kuvura indwara ziterwa na diyabete, umubyibuho ukabije, n'indwara y'umwijima idafite inzoga.
Umwanzuro
Nkibintu bitatu byitwa agonist, Retatrutid ifite amasezerano yo kuvura indwara ziterwa na metabolike.
Inkomoko
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[5] Doggrell S A. Ese retatrutide (LY3437943), GLP-1, GIP, na glucagon reseptor agonist intambwe yatewe mukuvura diyabete n'umubyibuho ukabije? [J]. Igitekerezo cyinzobere ku biyobyabwenge byiperereza, 2023.32 (5): 355-359.DOI: 10.1080 / 13543784.2023.2206560.
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