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 metabolisme ukomeje kwiyongera ku isi yose, gushakisha imiti ivura neza byahindutse ingingo ishyushye mu rwego rw'ubuvuzi. Maz, nk'igitabo gishya cya reseptor agonist, irashobora 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, itanga amahirwe mashya yo kuvura indwara ziterwa na metabolike.
Igishushanyo 1 Imiterere yimiti ya Maz.
Incamake ya Maz
Maz 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 Maz. 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, Maz 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 Gastric: Maz ikora reseptor ya GLP-1, ikora kuri sisitemu yo mu nda ya gastrointestinal kugirango igabanye ubusa gastric. 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 Maz, 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 Maz, izi ngaruka zo kwamamaza ntizizamura gusa glucose yamaraso ahubwo zigera no kugenzura neza glucose yamaraso binyuze mumikoranire hamwe ningaruka zo gukora reseptor ya 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
Maz icyarimwe ikora reseptor zombi za GLP-1 hamwe 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 Maz ifite ingaruka zikomeye zo kugabanya ibiro. Mu bushakashatsi bwibanze ku bantu bakuze bafite umubyibuho ukabije cyangwa umubyibuho ukabije mu, ibyumweru 24 byo kuvura Maz (hamwe na dose ntarengwa ya mg 6) byatumye impuzandengo yo kugabanya ibiro 6.7% –11.3%, mugihe itsinda rya placebo ryiyongereyeho 1.0%. Mu matsinda atandukanye, Maz 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 ryitabiriwe n’abitabiriye 680, Maz yerekanye inyungu ikomeye kurenza umwanya wa perezidansi mu kugabanya ibiro, hamwe n’itandukaniro rinini (MD) rya -6.22% (95% intera y'icyizere [CI]: -8.02% kugeza -4.41%).
Igishushanyo cya 2 Uburemere bwumubiri. 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 bafite metabolism yo mu bwoko bwa 2: Ku barwayi bafite metabolism yo mu bwoko bwa 2, Maz igabanya neza hemoglobine A1c (HbA1c) no kwiyiriza ubusa mu maraso glucose. Mu isuzuma rishingiye ku bushake, rihumye-rihumye, rigenzurwa na perezidansi yo mu cyiciro cya 2 cy’amavuriro, abarwayi bafite metabolism yo mu bwoko bwa 2 bahawe imiti ya Maz (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 <0.0001). Abarwayi nabo bagabanutse cyane muburemere bwumubiri, hamwe nimpuzandengo yijanisha ryerekana isano iri hagati yimiti, igera kuri -7.1%.
Ibyiza mugutunganya glucose yamaraso: Maz ntagabanya 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: Maz igabanya umuvuduko wamaraso wa sisitemu na diastolique. Isesengura ritunganijwe hamwe na meta-isesengura byerekana ko ugereranije na placebo, Maz igabanya umuvuduko wamaraso wa systolique kubitandukanya (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 Maz, harimo kunoza imikorere ya endoteliyale yimitsi, kugabanya imiyoboro y'amaraso ya periferique, no kugenzura amazi-sodium.
Amabwiriza ya Lipid: Maz 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 Maz (buri minsi 3) byagabanije cyane urugero rwa aside irike (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, Maz yahinduye impyiko za histopathologique yimbeba muri 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 Maz. Mu igeragezwa ryateganijwe, rigenzurwa na platbo, inshuro nyinshi kuzamura icyiciro cya 1b, abantu bakuru bafite ibiro byinshi cyangwa umubyibuho ukabije bahawe dosiye zitandukanye za Maz (kugeza kuri mg 10). Ibisubizo byerekanaga ko Maz yihanganiye cyane muri uru rwego, nta bintu bibi byavuzwe, kandi byagaragaye ko gutakaza ibiro byagaragaye.
Icyiciro cya 2 Ikigeragezo cyamavuriro: Ikigeragezo cya 2 cyamavuriro cyarushijeho kwemeza imikorere numutekano bya Maz mubantu batandukanye. Mu cyiciro cya 2 cyibasiye abarwayi b’abashinwa bafite metabolism yo mu bwoko bwa 2, Maz yerekanye ingaruka zikomeye mukugabanya HbA1c nuburemere bwumubiri, hamwe numutekano ugereranije nitsinda rya placebo. Ibisubizo bibi byakunze kugaragara cyane cyane byoroheje kandi bitagereranywa gastrointestinal reaction, nka diyare na isesemi. Mu cyiciro cya 2 cyibanda ku bantu bakuze bafite umubyibuho ukabije cyangwa umubyibuho ukabije, ibyumweru 24 byo kuvura Maz (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 gakondo ya GLP-1 yakira agoniste, Maz 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, Maz yageze ku gutakaza ibiro kurenza GLP-1 yakira reseptor agoniste mugihe kimwe cyo kuvura kandi yerekanaga ituze ryinshi mugucunga glucose.
Ugereranije n’indi miti igabanya ubukana: Ugereranije n’imiti gakondo ya antidiabete yo mu kanwa, Maz ntabwo igabanya glucose yamaraso gusa ahubwo inatanga inyungu zinyongera nko kugabanya ibiro hamwe no kunoza ibimenyetso byimitsi yumutima.
Umwanzuro
Nka GLP-1 / glucagon dual reseptor agonist, Maz igera ku buryo bunonosoye bwo guhindura ingufu za metabolisme, glucose yamaraso, umuvuduko wamaraso, hamwe na lipide yamaraso icyarimwe ikora ibintu bibiri byingenzi byakira imiti igabanya ubukana, ikagaragaza ingaruka zikomeye kandi zikomeye zo kuvura kuruta agoniste imwe. Maz afite amasezerano akomeye kubibazo bitandukanye byo guhindagurika, harimo umubyibuho ukabije, metabolism yo mu bwoko bwa 2, na hyperuricemia.
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
[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:
