Na Cocer Peptides 
hashize amezi 2
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.
Mu gihe umubare w'indwara ziterwa na metabolike nk'umubyibuho ukabije, umubyibuho ukabije, na diyabete ukomeje kwiyongera ku isi yose, gushakisha imiti ivura neza byahindutse ingingo ishyushye mu rwego rw'ubuvuzi. Mazdutide, nk'igitabo gishya cya reseptor agonist, gishobora icyarimwe gukora reseptor ya GLP-1 hamwe na reseptor ya glucagon, kandi biteganijwe ko izagira uruhare rudasanzwe mu kugabanya ibiro no kurwanya isukari mu maraso, bitanga amahirwe mashya yo kuvura indwara ziterwa na metabolike.
Igishushanyo 1 Imiterere yimiti ya Mazdutide.
Incamake ya Mazdutide
Mazdutide ni GLP-1 / glucagon dual reseptor agonist, imiti mishya yo kuvura indwara ziterwa na metabolike. Mu myaka mike ishize, iterambere ryibiyobyabwenge byibasira indwara ziterwa na metabolike ryakomeje gutera imbere. GLP-1 reseptor agonist na glucagon reseptor agonist bagaragaje ingaruka zimwe na zimwe zo kuvura iyo zikoreshejwe wenyine, ariko kandi zifite aho zigarukira. Kugira ngo bashake uburyo bwiza bwo kuvura, abashakashatsi bibanze ku guteza imbere ibiyobyabwenge bishobora gukora ku ntego nyinshi icyarimwe, biganisha ku ishyirwaho rya Mazdutide. Igikorwa cyiterambere cyacyo cyakorewe ubushakashatsi bwibanze kandi bugerageza ibyiciro byinshi byamavuriro, buhoro buhoro byemeza umutekano wacyo nibikorwa byiza.
Uburyo bwibikorwa
(1) Gukora kwa GLP-1
Kugena amaraso glucose homeostasis: GLP-1 ni imisemburo ya peptide isohoka mu ngirangingo L. Nyuma yo gukora reseptor ya GLP-1, Mazdutide igenga glucose yamaraso binyuze munzira nyinshi. Itera imisemburo ya insuline ikorwa na selile pancreatic β selile, ikongerera insuline ibyiyumvo, bityo kwihutisha gufata no kuyikoresha, no kugabanya glucose yamaraso. Irinda gusohora glucagon kuva selile pancreatic α selile kandi igabanya umusaruro wa glucose ya hepatike, bikarinda glucose glucose.
Gutinda Gusohora Gastrici: Mazdutide ikora reseptor ya GLP-1, ikora kuri sisitemu yo mu nda ya gastrointestinal kugirango igabanye ubusa. Ibi byongera ibiryo mu gifu, byongera guhaga no kugabanya ibiryo, bityo bigafasha kugenzura ibiro.
Kugena ubushake bwo kurya: Nyuma yo gukora reseptor ya GLP-1, ibimenyetso byoherezwa muri sisitemu yo hagati yo hagati, bigakorera kuri centre yo kugaburira hypothalamic kugirango bigabanye gusohora kwa neuropeptide ifitanye isano no kurya, nko kugabanya imvugo ya neuropeptide Y (NPY) no kongera imvugo ya poropiomelanocortine (POMC), bityo bigatuma umuntu yumva yuzuye kandi agaburira ibiryo.
(2) Gukora reseptor ya glucagon
Guteza imbere gukoresha ingufu: Iyo reseptor ya glucagon ikozwe na Mazdutide, itera kugabanuka kwamavuta hamwe na okiside ya aside irike, byongera ingufu zikoreshwa. Byongeye kandi, igenga imvugo ya poroteyine 1 (UCP1) idatezimbere, igatera thermogenezi mu ngingo ya adipose yijimye, bikarushaho kongera imbaraga mu mibiri y’umubiri no gufasha kugabanya ibiro.
Kugenga glucose metabolism: Gukora reseptor ya glucagon itera hepatike glycogenolysis na gluconeogenez. Nyamara, bitewe na Mazdutide, izi ngaruka zo kwamamaza ntizizamura gusa glucose yamaraso ahubwo zigera no kugenzura neza glucose yamaraso binyuze mumikoranire hamwe ningaruka ziterwa na GLP-1. Iyo amaraso ya glucose ari menshi, ingaruka ya hypoglycemic yahujwe no gukora reseptor ya GLP-1 iriganje; iyo amaraso ya glucose ari make, ingaruka ya hyperglycemic yahujwe no gukora glucagon reseptor ikora irinda hypoglycemia.
(3) Uburyo bukoreshwa
Mazdutide icyarimwe ikora GLP-1 yakira na glucagon. Inzira zerekana ibimenyetso zikorwa naba reseptors bombi zikorana hamwe kugirango zigire ingaruka zuzuye kandi zikomeye zo kugenzura metabolike. Ku bijyanye no kugabanya ibiro, ibikorwa bya GLP-1 byakira bigabanya gufata ingufu mu guhagarika ubushake bwo kurya no gutinda gusiba gastric, mu gihe gukora glucagon reseptor biteza imbere gukoresha ingufu. Igikorwa cyo guhuza ibikorwa byombi byakira neza bigabanya kugabanya ibiro. Kubijyanye no kugenzura amaraso glucose, ingaruka ziterwa no kwakirwa byombi zuzuzanya kugirango glucose yamaraso ibe murwego rusanzwe kandi irinde ihindagurika rikabije.
3. Ingaruka z'umubiri
(1) Ingaruka zo Gutakaza Ibiro
Ibimenyetso bya Clinical: Ibigeragezo byinshi byamavuriro byagaragaje ko Mazdutide igira ingaruka zikomeye zo kugabanya ibiro. Mu bushakashatsi bwibanze ku bantu bakuze bafite umubyibuho ukabije cyangwa umubyibuho ukabije muri, ibyumweru 24 byo kuvura Mazdutide (hamwe na dose ntarengwa ya mg 6) byatumye igabanuka ry’ibiro 6.7% –11.3%, mu gihe itsinda rya placebo ryiyongereyeho 1.0%. Mu matsinda atandukanye, Mazdutide kuri 4.5 mg na mg 6 yerekanye ingaruka zigaragara zo kugabanya ibiro, hamwe nubuvuzi butandukanye ugereranije na placebo kuva kuri -7.7% kugeza -12.3% (P <0.0001). Mu isubiramo rifatika hamwe na meta-isesengura ririmo 680 bitabiriye amahugurwa, Mazdutide yerekanye inyungu ikomeye kurenza umwanya wa perezidansi mu kugabanya ibiro, hamwe n’itandukaniro rito (MD) rya -6.22% (95% intera yicyizere [CI]: -8.02% kugeza -4.41%).
Igishushanyo cya 2 Uburemere bwibikorwa byumubiri. ihinduka ryijanisha riva muburemere muburemere bwumubiri mugihe cyicyumweru 24. b Ihinduka ryijanisha riva muburemere muburemere bwumubiri mugihe runaka.
(2) Ingaruka zo Glycemic
Ingaruka ku barwayi barwaye diyabete yo mu bwoko bwa 2: Ku barwayi barwaye diyabete yo mu bwoko bwa 2, Mazdutide igabanya neza hemoglobine A1c (HbA1c) no kwiyiriza ubusa glucose y'amaraso. Mu isuzuma rishingiye ku bushake, rihumye-rihumye, rigenzurwa na platbo yo mu cyiciro cya 2 cy’amavuriro, abarwayi ba diyabete yo mu bwoko bwa 2 bahawe imiti ya Mazdutide (ku gipimo ntarengwa cya mg 6) mu byumweru 20, bagaragaje impinduka mpuzandengo muri HbA1c kuva kuri -1.41% kugeza kuri -1,67%, mu gihe itsinda rya placebo ryerekanye ihinduka rya 0.03%, hamwe n’itandukaniro rikomeye ry’imibare ugereranije na placebo (P <0.000). Abarwayi nabo bagabanutse cyane muburemere bwumubiri, hamwe nimpuzandengo yijanisha ryerekana isano iri hagati yimiti, igera kuri -7.1%.
Ibyiza mugutunganya glucose yamaraso: Mazdutide ntigabanya gusa glucose yamaraso ahubwo inatezimbere glucose yamaraso kandi igabanya ibyago byo kwandura hypoglycemic. Ugereranije n’imiti gakondo igabanya ubukana bwa antidiabete, uburyo bwayo bubiri bwa reseptor agonist bwibikorwa bigera ku buryo bwuzuye kandi bwuzuye bwamaraso ya glucose, bityo bikazamura imibereho y’abarwayi ndetse n’igihe kirekire.
(3) Ingaruka ku bipimo by'umutima n'imitsi
Kugenzura umuvuduko wamaraso: Mazdutide igabanya umuvuduko wamaraso wa systolique na diastolique. Isesengura ritunganijwe hamwe na meta-isesengura ryerekana ko ugereranije na placebo, Mazdutide igabanya umuvuduko wamaraso wa systolique itandukaniro ugereranije (MD) ya -7.57 mmHg (95% CI: -11.17 kugeza kuri -3,98 mmHg); kugabanya umuvuduko wamaraso wa diastolique, MD yari -2,98 mmHg (95% CI: -5,74 kugeza -0.22 mmHg). Ibi birashobora guterwa nuburyo bwinshi bwa Mazdutide, harimo kunoza imikorere ya endoteliyale yimitsi, kugabanya imiyoboro y'amaraso ya periferique, no kugenzura amazi-sodium.
Amabwiriza ya Lipid: Mazdutide igenga neza imyirondoro ya lipide. Igabanya cholesterol yose (MD = -16.82%, 95% CI: -24.52 kugeza -9.13%), triglyceride (MD = -43.29%, 95% CI: -61.57 kugeza -25.01%), hamwe na lipoproteine nkeya (MD = -17.07%, 95% CI: -25.54 kugeza kuri -8.60%) = -7.54%, 95% CI: -11.26 kugeza -3.83%). Izi ngaruka zifasha kugabanya ibyago byindwara zifata umutima nimiyoboro kandi bigira ingaruka zo kurinda sisitemu yumutima.
(4) Ingaruka kuri hyperuricemia
Ibimenyetso byubushakashatsi bwibikoko: Mu bushakashatsi bw’imbeba ya hyperuricemia (HUA), gutera inshinge 0,05 mg / kg na 0,075 mg / kg ya Mazdutide (buri minsi 3) byagabanije cyane urugero rwa serumu uric aside (SUA) mu mbeba. Ugereranije nitsinda rya HUA, urwego rwa SUA na serumu creatinine (SCr) rwaragabanutse cyane mumatsinda ya Maz-MD na Maz-HD, kandi proteine yinkari (U-Pro) nayo yagabanutse cyane mumatsinda ya Maz-MD. Byongeye kandi, Mazdutide yateje imbere impyiko za histopathologique yimbeba za HUA.
Igishushanyo 3 a: Guhinduka kwijana kuva muburemere muburemere bwumubiri mugihe. b: Umubare w'abitabira kugera ku ntego zo kugabanya ibiro.
Ubushakashatsi
(1) Iterambere ryikigereranyo
Ibigeragezo byambere byubuvuzi: Icyiciro cya mbere cyambere cyamavuriro cyasuzumye mbere na mbere umutekano, kwihanganira, ningaruka zambere za Mazdutide. Mu buryo buteganijwe, bugenzurwa na platbo, inshuro nyinshi kuzamura icyiciro cya 1b, abantu bakuru bafite ibiro byinshi cyangwa umubyibuho ukabije bahawe dosiye zitandukanye za Mazdutide (kugeza kuri mg 10). Ibisubizo byerekanaga ko Mazdutide yihanganiye cyane muri uru rwego, nta bintu bibi byavuzwe, kandi byagaragaye ko gutakaza ibiro byagaragaye.
Icyiciro cya 2 Igeragezwa ryamavuriro: Ikigeragezo cyamavuriro yicyiciro cya 2 cyarushijeho kwemeza imikorere numutekano bya Mazdutide mubantu batandukanye. Mu cyiciro cya 2 cyibasiye abarwayi b'Abashinwa barwaye diyabete yo mu bwoko bwa 2, Mazdutide yerekanye ingaruka zikomeye mu kugabanya HbA1c n'uburemere bw'umubiri, n'umutekano ugereranije n'itsinda rya placebo. Ibisubizo bibi byakunze kugaragara cyane cyane byoroheje kandi bitagereranywa gastrointestinal reaction, nka diyare na isesemi. Mu cyiciro cya 2 kigerageza abantu bakuze bafite umubyibuho ukabije cyangwa umubyibuho ukabije, ibyumweru 24 byo kuvura Mazdutide (kugeza kuri mg 6) byagaragaje ingaruka nziza zo kugabanya ibiro n'umutekano.
(2) Ubushakashatsi bugereranya nibindi biyobyabwenge
Ugereranije na GLP-1 yakira reseptor agoniste: Ugereranije na GLP-1 gakondo ya reseptor agoniste, Mazdutide irashobora kugira ingaruka zikomeye mugutakaza ibiro no kugenzura amaraso ya glucose bitewe nuburyo bubiri bwibikorwa bya GLP-1 hamwe na reseptor ya glucagon. Mu bushakashatsi bumwe na bumwe, Mazdutide yageze ku kugabanuka cyane kurenza GLP-1 yakira reseptor agoniste mugihe kimwe cyo kuvura kandi yerekanaga ituze ryinshi mugucunga glucose.
Ugereranije nindi miti igabanya ubukana: Ugereranije n’imiti gakondo ya antidiabete yo mu kanwa, Mazdutide ntabwo igabanya glucose yamaraso gusa ahubwo inatanga inyungu zinyongera nko kugabanya ibiro ndetse no kunoza ibimenyetso byimitsi yumutima.
Umwanzuro
Nka GLP-1 / glucagon dual reseptor agonist, Mazdutide igera ku kugenzura byimazeyo imbaraga za metabolisme yingufu, glucose yamaraso, umuvuduko wamaraso, hamwe na lipide yamaraso mugukoresha icyarimwe ibintu bibiri byingenzi byakira imiti igabanya ubukana, byerekana ingaruka zikomeye kandi zikomeye zo kuvura kuruta agoniste imwe. Mazdutide ifite amasezerano akomeye kubibazo bitandukanye byo guhindagurika, harimo umubyibuho ukabije, diyabete yo mu bwoko bwa 2, na hyperuricemia.
Inkomoko
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[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
[5] Ji L, Gao L, Jiang H, n'abandi. Umutekano ningirakamaro bya GLP-1 na glucagon reseptor dual agonist mazdutide (IBI362) mg 9 na mg 10 mubantu bakuru b'Abashinwa bafite umubyibuho ukabije cyangwa umubyibuho ukabije: Ikigereranyo cyateganijwe, kigenzurwa na platbo, cyinshi-kizamuka-dose icyiciro cya 1b [J]. Eclinicalmedicine, 2022,54: 101691.DOI: 10.1016 / j.eclinm.2022.101691.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
