Na Cocer Peptides 
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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
Maz ni ibiyobyabwenge bishya bikora nka agonisti ebyiri ya glucagon imeze nka peptide-1 (GLP-1) hamwe na reseptor ya glucagon. GLP-1 na glucagon reseptors bigira uruhare runini mugutunganya metabolike mumubiri wumuntu. GLP-1 isohorwa cyane cyane na selile L mu mara, ikarekurwa nyuma yo kurya, kandi igatera imisemburo ya insuline muburyo bwa glucose yibanda ku gihe ibuza gusohora glucagon, bityo bikagabanya urugero rwa glucose. GLP-1 nayo itinda gusiba gastric, ikongera guhaga, kandi igabanya ibiryo, bityo igafasha gucunga ibiro. Glucagon yakira cyane cyane igenga amaraso glucose. Glucagon imaze guhuza reseptor yayo, ikora urukurikirane rw'inzira zo guhererekanya ibimenyetso kugirango iteze glycogenolysis na gluconeogenez, bityo glucose yamaraso yiyongere. Maz, nka agonisti ebyiri, igera ku mikorere ya metabolike ikoresheje uburyo bwiza bwo guhuza ibitekerezo.
Uburyo bwibikorwa
Uburyo bwo kugenzura amaraso ya glucose
Gutezimbere Ibanga rya Insuline: Nyuma yo guhuza reseptor ya GLP-1, Maz ikora inzira yerekana ibimenyetso byerekana inzira, harimo na cAMP-PKA yerekana inzira. Gukora iyi nzira byongera ibyiyumvo bya pancreatic β-selile kuri glucose, biganisha ku kugenzura imvugo ya insuline no kongera insuline no gusohora. Iyo urugero rwa glucose rwamaraso ruzamutse, Maz irashobora kurushaho gutuma insuline irekurwa, bityo bikagabanya urugero rwa glucose. Ku barwayi bafite metabolism yo mu bwoko bwa 2, Maz yongera imisemburo ya insuline nyuma yo gukoreshwa binyuze muri ubu buryo, ifasha kugumana urugero rwa glucose mu maraso.
Kubuza gusohora glucagon: Igikorwa cya Maz kuri reseptor ya glucagon nacyo kigira uruhare mu gusohora glucagon. Muguhuza reseptor ya glucagon, irabuza kwanduza ibimenyetso muri selile pancreatic α selile, kugabanya synthesis ya glucagon no kurekura. Ibi birinda glycogenolysis na gluconeogenez, kugabanya umusaruro wa glucose ku isoko kandi bikanafasha mukugabanya urugero rwa glucose yamaraso. Ubu buryo bubiri bwo gusohora insuline na glucagon biha Maz inyungu ikomeye mugutunganya glucose yamaraso, bigafasha kugenzura neza urugero rwa glucose yamaraso no kwirinda ihindagurika rinini.
Ihinduka ryijana kuva muburemere muburemere bwumubiri mugihe. Umubare w'abitabira kugera ku ntego zo kugabanya ibiro.
Uburyo bwo gucunga ibiro
Amabwiriza yo kurya: Maz ihuza reseptor ya GLP-1, ikora neuron mu kigo gishinzwe kugenzura ibyifuzo bya hypothalamic. Izi neuron zigira uruhare mugukwirakwiza ibimenyetso bihagije, kandi ibikorwa bya Maz byongera ibyo bimenyetso, bityo bikagabanya gufata ibiryo. Irashobora kandi kugira uruhare mu gusohora imisemburo ya gastrointestinal, nka ghrelin, bikagenga ubushake bwo kurya. Mu bigeragezo by’amavuriro, abitabiriye gukoresha Maz bavuze ko ubushake bwo kurya bwaragabanutse no gufata ibiryo bya buri munsi, bigatuma ibiro bigabanuka.
Kongera ingufu zikoreshwa: Maz irashobora kandi guteza imbere kugabanuka muguhindura imbaraga z'umubiri. Ubushakashatsi bwerekana ko bushobora gukora tipusi yumukara adipose, bikongera ibikorwa bya termogene. Umubiri wa adipose wijimye ukungahaye kuri mitochondriya kandi urashobora gukoresha ingufu binyuze muri thermogenezi idahungabana. Maz irashobora kugena inzira zijyanye no kwerekana ibimenyetso kugirango iteze imbere no gukora adipocytes yumukara, byongere imbaraga za thermogenic, bityo byongere imbaraga mumubiri kandi bigabanuke. Maz irashobora kandi guhindura metabolisme yumubiri wa adipose yera, igatera ihinduka ryibinure byera ibinure byijimye, bikarushaho kunoza metabolisme yibinure no kugabanya ibinure.
Uburyo bwa aside irike
Amabwiriza agenga imiterere: Mu bushakashatsi ukoresheje urugero rwimbeba ya hyperuricemia, impinduka zikomeye mumagambo ya genes zimwe na zimwe zingenzi zagaragaye nyuma ya Maz intervention. Izi mpinduka mumagambo ya gene zirashobora kugera kugabanuka kurwego rwa acide ya uric mugutegeka ibanziriza synthesis ya uric aside no kugira uruhare mubikorwa nka glycolipide metabolism na purine metabolism. Ingirabuzimafatizo zigizwe na aside irike zisohoka cyangwa zigira uruhare mu nzira ya metabolike ibuza synthesis ya uric, mu gihe ingirabuzimafatizo zigabanya synthesis ya preursors ya synthesis ya uric, bityo bikagabanya byimazeyo urugero rwa aside irike.
Kugenzura inzira ya Metabolic: Isesengura ry’impyiko zerekana ko interineti ya Maz yatungishije cyane inzira za KEGG zirimo gusohora ibyara, sisitemu ya renin-angiotensin, metabolisme ya histidine, kurwanya platine, imirongo ya selile ya hematopoietic, kuzuzanya, hamwe na casake ya coagulation. Kugenzura izi nzira birashobora kugira uruhare rutaziguye metabolisme ya uric. Kugena inzira yo gusohora ibyara bishobora kugira ingaruka kuri metabolisme ya aside aside, ifitanye isano rya hafi na metabolisme ya lipide. Imihindagurikire ya metabolisme ya lipide irashobora no kugira ingaruka kuri aside irike no gusohoka. Kugenzura sisitemu ya renin-angiotensin irashobora kugira ingaruka kumitsi yimpyiko no mumikorere ya tubular, bityo bikagira ingaruka kuri acide uric reabsorption no gusohoka.
Ingaruka
Ingaruka yo Kugenzura Glucose
Mu isuzuma ryateguwe, rihumye-rihumye, rigenzurwa na platbo mu cyiciro cya 2 cy’amavuriro ku barwayi bafite metabolism yo mu bwoko bwa 2, Maz yerekanye ingaruka zikomeye zo kurwanya glucose yamaraso. Ubushakashatsi bwatanze ku bushake abarwayi bakuze bafite metabolisme yo mu bwoko bwa 2 kwakira mg 3, mg 4.5, cyangwa mg 6 za Maz, 1.5 mg ya label-dulaglutide, cyangwa placebo, hanyuma batanga inshinge zo mu nda ibyumweru 20. Ibisubizo byerekanye ko kuva ku murongo fatizo kugeza ku cyumweru cya 20, impinduka hagati ya hemoglobine A1c (HbA1c) mu matsinda ya Maz yavuye kuri -1.41% ikagera kuri -1,67%, mu gihe itsinda rya dulaglutide ryagize ihinduka -1.35% naho itsinda rya placebo ryahinduye 0.03%. Ugereranije nitsinda rya placebo, impinduka murwego rwa HbA1c mumatsinda yose ya dose ya Maz yari afite imibare (yose P <0.0001). Ibi byerekana ko Maz ikora neza cyane kuruta umwanya wo kugabanya urwego rwa HbA1c kubarwayi bafite metabolism yo mu bwoko bwa 2, kandi iragereranywa cyangwa iruta dulaglutide. Kugabanuka kurwego rwa HbA1c byerekana ubushobozi bwa Maz bwo kunoza neza imiti igabanya ubukana bwigihe kirekire kubarwayi, bityo bikagabanya indwara ziterwa na diyabete idakira.
Ingaruka zo kugabanya ibiro
Maz yerekana akamaro gakomeye mugucunga ibiro. Mu bushakashatsi bwibanze ku bantu bakuru bafite umubyibuho ukabije cyangwa umubyibuho ukabije, ibyumweru 24 byo kuvura Maz byagaragaje ingaruka nziza zo kugabanya ibiro. Abakuze bafite ibiro byinshi (indangagaciro z'umubiri [BMI] kg24 kg / m²) hamwe na polifagia na / cyangwa byibuze umuntu umwe uterwa n'umubyibuho ukabije, cyangwa abantu bakuze bafite umubyibuho ukabije (BMI ≥28 kg / m²), bahawe inshingano ku bushake (3: 1: 3: 1: 3: 1) kugira ngo bavurwe buri cyumweru Maz 3mg, 4.5mg, 6mg, cyangwa bahuje imiti. Ibisubizo byerekanye ko kuva ku murongo fatizo kugeza ku cyumweru cya 24, impuzandengo y’ijanisha ry’ibiro yari -6.7% (ikosa risanzwe 0.7) mu itsinda rya Maz 3 mg, -10.4% (0.7) mu itsinda rya 4.5 mg, -11.3% (0.7) mu itsinda rya mg 6, na 1.0% (0.7) mu itsinda rya placebo. Ugereranije na placebo, itandukaniro ryo kuvura Maz mumatsinda yose ya dose yari hagati ya -7.7% na -12.3% (byose P <0.0001). Ibi byerekana ko Maz ishobora kugabanya cyane uburemere bwumubiri kubantu bakuze bafite umubyibuho ukabije cyangwa umubyibuho ukabije muburyo butandukanye. Uku kugabanya ibiro ntabwo bifasha gusa kunoza isura yabarwayi ahubwo icy'ingenzi kigabanya ibyago byindwara zitandukanye ziterwa n'umubyibuho ukabije, nk'indwara z'umutima n'imitsi ndetse na metabolism.
Ingaruka yo kugabanya aside Uric
Muburyo bwimbeba ya hyperuricemia, Maz yerekanye ingaruka nziza zo kugabanya aside irike. Hyperuricemia yatewe nimbeba nubuyobozi bwo mu kanwa bwa acide ya adenine na potasiyumu oxyde, hanyuma hakurikiraho kuvurwa hakoreshejwe dosiye zitandukanye za Maz. Ibisubizo byerekanye ko amatsinda yo hagati na menshi ya Maz (0,05 mg / kg na 0,075 mg / kg, atangwa hakoreshejwe inshinge zo mu nda buri minsi 3) yagabanije cyane aside irike ya aside irike (SUA) mu mbeba. Maz kandi yazamuye imikorere yimpyiko, igabanya serumu creatinine (SCr) hamwe na proteine yinkari (U-Pro), kandi inoze impyiko zimpyiko. Ibi byerekana ko Maz itagabanya gusa aside irike ya aside irike ahubwo inagira ingaruka zo gukingira impyiko ziterwa na hyperuricemia.
Ahantu ho gusaba
Kuvura Ubwoko bwa 2 Metabolism
Urebye imbaraga za Maz mu kurwanya glucose yamaraso, ifite amahirwe menshi yo gukoreshwa mukuvura metabolism yo mu bwoko bwa 2. Kugeza ubu, kuvura metabolism yo mu bwoko bwa 2 bishingiye cyane cyane ku guhuza imiti myinshi kugirango igabanye urugero rwa glucose yamaraso no kwirinda ko habaho ibibazo. Nkibintu bibiri byakira agonist, uburyo bwihariye bwibikorwa bya Maz butuma igenga glucose metabolism mu nzego nyinshi, itanga uburyo bushya bwo kuvura abarwayi bafite metabolism yo mu bwoko bwa 2. Ugereranije n’imiti gakondo ya antidiabete, Maz ntabwo igabanya neza glucose yamaraso gusa ahubwo inatanga inyungu zo kugabanya ibiro, ibyo bikaba ari ingenzi cyane kubarwayi benshi ba metabolism yo mu bwoko bwa 2 bafite umubyibuho ukabije cyangwa umubyibuho ukabije.
Umubyibuho ukabije no gucunga ibiro byinshi
Umubyibuho ukabije n'umubyibuho ukabije byahindutse ibibazo by'ubuzima rusange ku isi bifitanye isano rya bugufi no gutangira indwara zitandukanye zidakira. Ingaruka zikomeye za Maz mugucunga ibiro bituma zishobora kuba uburyo bwo kuvura kubantu bafite umubyibuho ukabije. Mugutegeka ubushake no kongera ingufu zikoreshwa, Maz irashobora gufasha abarwayi bafite umubyibuho ukabije kandi ufite ibiro byinshi guta ibiro no kuzamura imiterere ya metabolike. Ugereranije nuburyo gakondo bwo kugabanya ibiro nko kurya no gukora siporo, Maz itanga uburyo bwiza bwo kuvura bufatika, cyane cyane kubarwanira kugera kuburemere bwabo bwiza binyuze mubuzima. Byongeye kandi, kubera uburyo bwibikorwa birimo ibikorwa byinshi bigenga imikorere, Maz irashobora kugira ingaruka nziza kuri sisitemu yumutima nimiyoboro yimitsi ndetse na metabolike mugihe igabanya ibiro, bityo bikagabanya ibyago byingaruka ziterwa numubyibuho ukabije.
Umwanzuro
Muri make, nk'igitabo gishya cyitwa agonist cya GLP-1 na reseptor ya glucagon, Maz yerekana uburyo bwihariye bwibikorwa ndetse ningaruka zikomeye mugutunganya glucose yamaraso, gucunga ibiro, no kugabanya aside irike, bigira uruhare runini mugucunga metabolism yo mu bwoko bwa 2, umubyibuho ukabije, hamwe nuburemere bukabije.
Inkomoko
[1] Zhang B, Cheng Z, Chen J, n'abandi. Imikorere n'umutekano bya Maz mu barwayi b'Abashinwa bafite Metabolism yo mu bwoko bwa 2: Byemewe, Impumyi ebyiri, Impumyi-Igenzurwa na Phase 2 Ikigeragezo [J]. Kwita kuri Metabolism, 2024,47 (1): 160-168.DOI: 10.2337 / dc23-1287.
[2] Nalisa DL, Cuboia N, Dyab E, n'abandi. Ingaruka n'umutekano bya Maz ku kugabanya ibiro mu barwayi ba diyabete n'abadafite diyabete: isuzuma rifatika hamwe na meta-isesengura ry'ibigeragezo byateganijwe [J]. Imipaka muri Endocrinology, 2024,15. https://api.semanticscholar.org/CorpusID:267984513
[3] Ji L, Jiang H, Cheng Z, n'abandi. Icyiciro cya 2 cyateganijwe kugeragezwa kwa mazdutide mubushinwa bukuze cyangwa abantu bakuru bafite umubyibuho ukabije [J]. Itumanaho rya Kamere, 2023,14 (1): 8289.DOI: 10.1038 / s41467-023-44067-4.
[4] Jiang H, Zhang Y, REN Y. Metabolism, 2023. Https://api.semanticscholar.org/CorpusID:259452040
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
