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
Mazdutide 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. Mazdutide, nka agoniste ebyiri, igera ku mikorere ya metabolike ikoresheje uburyo bwubwenge.
Uburyo bwibikorwa
Uburyo bwo kugenzura amaraso ya glucose
Gutezimbere Ibanga rya Insuline: Nyuma yo guhuza reseptor ya GLP-1, Mazdutide 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, Mazdutide irashobora kurushaho gutuma insuline irekurwa, bityo bikagabanya urugero rwa glucose yamaraso. Ku barwayi barwaye diyabete yo mu bwoko bwa 2, Mazdutide yongerera insuline nyuma ya nyuma ya insuline binyuze muri ubu buryo, ifasha kugumana urugero rwa glucose mu maraso.
Kubuza gusohora glucagon: Igikorwa cya Mazdutide ku 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 Mazdutide 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: Mazdutide ihuza reseptor ya GLP-1, ikora neuron mukigo gishinzwe kugenzura ibyifuzo bya hypothalamic. Izi neuron zigira uruhare mugukwirakwiza ibimenyetso bihagije, kandi ibikorwa bya Mazdutide 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 Mazdutide bavuze ko ubushake bwo kurya bwagabanutse kandi ibiryo bigabanuka buri munsi, bigatuma ibiro bigabanuka.
Kongera ingufu zikoreshwa: Mazdutide irashobora kandi guteza imbere kugabanuka muguhindura imbaraga z'umubiri metabolism. 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. Mazdutide irashobora kugena inzira zijyanye no kwerekana ibimenyetso kugirango iteze imbere no gukora adipocytes yumukara, byongere imbaraga za thermogeneque, bityo byongere imbaraga mumubiri kandi bigabanuke. Mazdutide irashobora kandi guhindura metabolisme yumubiri wa adipose yera, igatera ihinduka ryamavuta yera kumavuta yumukara, bikarushaho kunoza metabolisme yibinure no kugabanya ibinure.
Uburyo bwa aside irike
Kugena imiterere ya Gene: Mu bushakashatsi ukoresheje urugero rwimbeba ya hyperuricemia, impinduka zikomeye mumagambo ya genes zimwe na zimwe zingenzi zagaragaye nyuma yo gutabarwa kwa Mazdutide. 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 metabolike: Isesengura ry’impyiko zerekana ko interineti ya Mazdutide yatungishije cyane inzira za KEGG zirimo ururenda rw’imyunyu ngugu, sisitemu ya renin-angiotensin, metabolism ya histidine, kurwanya platine, imirongo ya selile ya hematopoietic, kuzuzanya, hamwe na kasike 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 barwaye diyabete yo mu bwoko bwa 2, Mazdutide yerekanye ingaruka zikomeye zo kurwanya amaraso glucose. Ubushakashatsi bwatanze ku bushake abarwayi bakuze barwaye diyabete yo mu bwoko bwa 2 kwakira mg 3, mg 4.5, cyangwa mg 6 za Mazdutide, 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 Mazdutide 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 Mazdutide yari afite imibare ikomeye (yose P <0.0001). Ibi byerekana ko Mazdutide ikora neza cyane kuruta umwanya wa plato mukugabanya urugero rwa HbA1c kubarwayi barwaye diyabete yo mu bwoko bwa 2, kandi igereranywa cyangwa iruta dulaglutide. Kugabanuka kurwego rwa HbA1c byerekana ubushobozi bwa Mazdutide bwo kunoza neza igenzura ryigihe kirekire kubarwayi, bityo bikagabanya indwara ziterwa na diyabete idakira.
Ingaruka zo kugabanya ibiro
Mazdutide yerekana imikorere ikomeye mugucunga ibiro. Mu bushakashatsi bwibanze ku bantu bakuru bafite umubyibuho ukabije cyangwa umubyibuho ukabije, ibyumweru 24 byo kuvura Mazdutide 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 ufite umubyibuho ukabije, cyangwa abantu bakuru bafite umubyibuho ukabije (BMI ≥28 kg / m²), bahawe inshingano ku bushake (3: 1: 3: 1: 3: 1) kugira ngo bavurwe buri cyumweru Mazdutide 3mg, 4.5mg, 6mg. 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 Mazdutide 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 Mazdutide mumatsinda yose ya dose yari hagati ya -7.7% na -12.3% (byose P <0.0001). Ibi byerekana ko Mazdutide ishobora kugabanya cyane uburemere bwumubiri kubantu bakuze bafite umubyibuho ukabije cyangwa umubyibuho ukabije muburyo butandukanye. Uku kugabanya ibiro ntabwo bifasha gusa kunoza isura yumubiri gusa ahubwo cyane cyane bigabanya ibyago byindwara zitandukanye ziterwa numubyibuho ukabije, nkindwara zifata umutima na diabete.
Ingaruka yo kugabanya aside Uric
Muburyo bwimbeba ya hyperuricemia, Mazdutide yerekanye ingaruka nziza zo kugabanya aside irike. Hyperuricemia yatewe n'imbeba n'ubuyobozi bwo mu kanwa bwa acide ya adenine na potasiyumu oxyde, hanyuma hakurikiraho kuvurwa hakoreshejwe dosiye zitandukanye za Mazdutide. Ibisubizo byerekanaga ko amatsinda yo hagati na menshi ya Mazdutide (0,05 mg / kg na 0,075 mg / kg, atangwa hakoreshejwe inshinge zo munsi ya buri munsi 3) yagabanije cyane aside irike ya aside irike (SUA) mu mbeba. Mazdutide yanatezimbere imikorere yimpyiko, igabanya serumu creatinine (SCr) hamwe na proteine yinkari (U-Pro), kandi inoze impyiko zimpyiko. Ibi byerekana ko Mazdutide itagabanya gusa aside irike ya serike ahubwo inagira ingaruka zo gukingira impyiko ziterwa na hyperuricemia.
Ahantu ho gusaba
Kuvura Diyabete yo mu bwoko bwa 2
Urebye akamaro gakomeye ka Mazdutide mukurwanya glucose yamaraso, ifite amahirwe menshi yo gukoreshwa mukuvura diyabete yo mu bwoko bwa 2. Kugeza ubu, kuvura diyabete yo mu bwoko bwa 2 bishingiye cyane cyane ku guhuza imiti myinshi kugira ngo igabanye urugero rwa glucose mu maraso no kwirinda ko habaho ibibazo. Nka agashya ka reseptor agonist, uburyo bwihariye bwibikorwa bya Mazdutide butuma igenga glucose metabolism mu nzego nyinshi, itanga uburyo bushya bwo kuvura abarwayi ba diyabete yo mu bwoko bwa 2. Ugereranije n’imiti gakondo ya antidiabete, Mazdutide ntagabanya gusa glucose yamaraso gusa ahubwo inatanga inyungu zo kugabanya ibiro, bikaba ari ngombwa cyane cyane kubarwayi ba diyabete 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 Mazdutide mugucunga ibiro bituma zishobora kuba uburyo bwo kuvura kubantu bafite umubyibuho ukabije. Mugutegeka ubushake bwo kurya no kongera ingufu zikoreshwa, Mazdutide 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, Mazdutide itanga uburyo bwiza bwo kuvura bufatika, cyane cyane kubarwanira kugera ku buremere bwabo bwiza binyuze mubuzima. Byongeye kandi, bitewe nuburyo bukoreshwa bwibikorwa birimo uburyo butandukanye bwo kugenzura imikorere, Mazdutide 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 hamwe na reseptor ya glucagon, Mazdutide yerekana uburyo bwihariye bwibikorwa ningaruka zikomeye mugutunganya glucose yamaraso, gucunga ibiro, no kugabanya aside irike, bigira uruhare runini mugucunga diyabete yo mu bwoko bwa 2, umubyibuho ukabije, hamwe nuburemere bukabije.
Inkomoko
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[2] Nalisa DL, Cuboia N, Dyab E, n'abandi. Imikorere n'umutekano bya Mazdutide ku kugabanya ibiro mu barwayi ba diyabete n'abadafite diyabete: isuzuma rifatika hamwe na meta-gusesengura 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.
] Diyabete, 2023. Https://api.semanticscholar.org/CorpusID:259452040
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