Na Cocer Peptides 
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INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBURANISHA 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 byemewe 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 GLP-1
GLP-1 ni glucagon nshyashya imeze nka peptide-1 reseptor agonist (GLP-1 RA). Glucagon imeze nka peptide-1 (GLP-1) ni imisemburo isanzwe isohoka mumubiri wumuntu igira uruhare runini mugutunganya glucose yamaraso. Iyo urugero rwa glucose rwamaraso ruzamutse, GLP-1 irekurwa kandi ikagenga glucose yamaraso binyuze muburyo butandukanye. Nyamara, ku barwayi ba diyabete, ururenda rwa GLP-1 akenshi ntiruhagije cyangwa ingaruka zarwo ntizihagije. GLP-1 ihuza reseptor ya GLP-1, yigana ingaruka zifatika za GLP-1, bityo ikagira ingaruka zo kuvura metabolism no gucunga ibiro.
Igicapo 1 Kuvura umubyibuho ukabije n'ingaruka zazo mu kugabanya ibiro
Uruhare rwa GLP-1 mu kuvura Diyabete
Gutezimbere Ibanga rya Insuline
Mugihe cyimiterere yumubiri, iyo glucose yamaraso yiyongereye, selile enteroendocrine mumara isohora GLP-1. GLP-1 ihuza reseptor ya GLP-1 hejuru ya selile pancreatic β selile, ikora urukurikirane rw'inzira zerekana ibimenyetso byongera insuline. GLP-1 irashobora kandi guhuza cyane na reseptor ya GLP-1 hejuru ya selile pancreatic β selile, itera insuline gusohora muburyo bwa glucose. Ibi bivuze ko iyo glucose yamaraso izamutse, GLP-1 itera neza kurekura insuline kugirango igabanye glucose yamaraso; iyo glucose yamaraso iri murwego rusanzwe, ingaruka zayo mugutezimbere insuline iba idakomeye, bityo bikagabanya ibyago byo kurwara hypoglycemia. Ubushakashatsi bwerekanye ko nyuma yo kuvurwa na GLP-1, urwego rw’abarwayi ba insuline rwiyongera cyane, kandi glucose yamaraso irashobora kugenzurwa neza.
Igishushanyo 2: Uburyo bwo hejuru bwibiro-buringaniye hamwe nuburyo bwo hasi, glucose-centric, na cardiometabolic. Ubuvuzi bushingiye kuri Incretin bumaze gukora murwego rwo hejuru.
Bitandukanye na insuline gakondo ya insuline, nka sulfonylureas, ihora itera ururenda rwa insuline hatitawe ku kigero cya glucose y’amaraso kandi ishobora kongera ibyago byo kurwara hypoglycemia, GLP-1 ya glucose-concentration iterwa na insuline yo mu maraso ituma igabanya neza urugero rwa glucose mu maraso mu gihe igabanya cyane indwara ya glucose y’amaraso.
Kubuza gusohora glucagon
Glucagon ni imisemburo isohorwa na pancreatic α selile izamura urugero rwa glucose yamaraso, ikora ibinyuranye na insuline. Ku barwayi ba diyabete, ururenda rwa glucagon akenshi ntirukumirwa nubwo urugero rwa glucose rwamaraso ruri hejuru. GLP-1 ikora kuri reseptor ya GLP-1 kuri selile pancreatic α selile kugirango ibuze glucagon. Iyo ururenda rwa glucagon rugabanutse, glycogenolysis yumwijima hamwe na gluconeogenezi yumubiri irahagarikwa, bikagabanya umusaruro wa glucose endogenous kandi bikagabanya urugero rwamaraso glucose. Abahanga bemeje ko mu bwoko bwa 2 metabolism abarwayi bavuwe na GLP-1, plasma glucagon igabanuka cyane, bikagabanya umusaruro wa glucose w’umwijima kandi bigira uruhare runini mu guhagarika urugero rw’amaraso glucose.
Gutinda gusiba gastric
GLP-1 ikora kuri reseptor ya GLP-1 mu nzira ya gastrointestinal kugirango igabanye ubusa gastric. Gusiba vuba gastrica bitera ibiryo kwinjira mu mara mato vuba, bigatuma umuvuduko wamaraso wiyongera vuba. Mugutinda gusiba gastric, ibiryo biguma mu gifu igihe kirekire kandi byinjira mu mara mato gahoro gahoro, bikaviramo kwinjiza glucose buhoro buhoro kandi bikarinda kwiyongera gukabije nyuma ya glucose yamaraso. Izi ngaruka zifasha kugumana urugero rwa glucose rwamaraso nyuma yo kugabanuka no kugabanya ihindagurika ryamaraso glucose. Mu bigeragezo bimwe na bimwe by’amavuriro, abarwayi bavuwe na GLP-1 bagize igabanuka rikabije ry’imisemburo y’amaraso ya glucose nyuma y’imihindagurikire y’imihindagurikire y’amaraso ya glucose, bituma ubwiza bw’amaraso bugabanuka muri rusange. Byongeye kandi, gutinda gusya kwa gastrici birashobora gutuma umuntu yumva yuzuye, agafasha kugabanya ibiryo bityo bigafasha mukurinda glucose yamaraso no gucunga ibiro kurundi ruhande.
Igishushanyo 3: Uburyo bwa GLP-1 bwo gucunga umubyibuho ukabije
Gutezimbere β-Akagari Imikorere
Indwara ya hyperglycemia idakira irashobora kwangiza selile pancreatic β selile, biganisha kumikorere gahoro gahoro. GLP-1 ntabwo igabanya isukari yamaraso gusa iteza imbere gusohora insuline ahubwo inarinda kandi igasana uturemangingo twa pancreatic β selile, bityo igahindura imikorere ya selile. Ubushakashatsi bwa siyansi bwerekanye ko GLP-1 ishobora gukora inzira zimwe na zimwe zerekana ibimenyetso byerekana inzira yo gukwirakwiza β-selile, ikabuza β-selile apoptose, bityo ikongera umubare n'imikorere ya β-selile. Mu bushakashatsi bw’inyamaswa ndetse n’ubushakashatsi bumwe na bumwe bw’ubuvuzi, byagaragaye ko nyuma yo gukoresha GLP-1, ubushobozi bwo gusohora insuline ya β selile bwongerewe imbaraga, kandi birwanya insuline. Ibi bifite akamaro kanini mukuvura igihe kirekire kuvura metabolism yo mu bwoko bwa 2, kuko bifasha kugabanya umuvuduko windwara no kugabanya ibyago byo kurwara diyabete.
Gushyira mu bikorwa GLP-1 mu kuvura Diyabete
GLP-1 ifite uburyo butandukanye bwo gukoresha muburyo bwo kuvura metabolism. Ku barwayi ba metabolism bo mu bwoko bwa 2 basuzumwe, niba glucose yamaraso itazamutse cyane kandi nta ngaruka zikomeye zigaragara cyangwa izindi ngaruka zikomeye, hashobora gutekerezwa monotherapy hamwe na GLP-1. Ubushakashatsi ku mavuriro bwerekana ko abarwayi bamwe basuzumwe bahuye n’igabanuka rikabije rya hemoglobine A1c (HbA1c) no gutakaza ibiro nyuma yigihe cyo kwivuza. Kurugero, murukurikirane rwa PIONEER yubushakashatsi, abarwayi bavuwe munzira ya GLP-1 yo mu kanwa bagabanutse cyane kurwego rwa HbA1c ugereranije nitsinda rya placebo, bafite umutekano mwiza no kwihanganira. Ibyiza byo kwivuza ni uko birinda ingaruka ziterwa n’imiti ijyanye no kuvura hamwe, kandi ubuyobozi bworoheje ugereranije bufasha kunoza uburyo bwo kuvura abarwayi.
GLP-1 irashobora kandi gukoreshwa hamwe nindi miti. Iyo uhujwe na metformin, ikaba ari imiti yambere kumurongo wa metabolism yo mu bwoko bwa 2, itezimbere insuline kandi igabanya umusaruro wa glucose hepatike. Iyi miti yombi ifite uburyo bwuzuzanya bwibikorwa, bigafasha kugenzura neza glucose yamaraso. Ubushakashatsi bwerekanye ko uku guhuza gahunda kurushaho kugabanya urwego rwa HbA1c kandi bikavamo kugabanuka cyane. Kurugero, mubigeragezo bimwe na bimwe byamavuriro, abarwayi bavuwe na metformine bongeyeho GLP-1 bagabanutse cyane kurwego rwa HbA1c ugereranije nabakomeje kwivuza metformin, hamwe no gutakaza ibiro, nta kwiyongera gukabije kwa hypoglycemia. Ubu buryo bukwiriye abarwayi bafite glucose yamaraso itagenzuwe bihagije hamwe na metformin monotherapy.
Ku barwayi bafite metabolisme yo mu bwoko bwa 2 bafite glucose yuzuye mu maraso kandi bakeneye ubuvuzi bwa insuline, kongera GLP-1 mu kuvura insuline birashobora kugabanya urugero rwa insuline. Mu kuvura insuline, abarwayi bakunze guhura nibibazo nko kongera ibiro ndetse no kongera ibyago byo kurwara hypoglycemia. Iyo ikoreshejwe hamwe, ingaruka za GLP-1 zo guteza imbere insuline no guhagarika imisemburo ya glucagon zirashobora guhindura imikoreshereze ya insuline, kugabanya dosiye, bityo bikagabanya ingaruka zo kongera ibiro na hypoglycemia. Kurugero, mubushakashatsi bumwe na bumwe bwamavuriro, abarwayi bongeyeho GLP-1 mubuvuzi bwabo bwa insuline bahuye nigabanuka ryikigereranyo cya dosiye ya insuline, hamwe no kugabanuka kurwego rwa HbA1c, kugabanuka ibiro, no kugabanuka kwinshuro za hypoglycemia.
GLP-1 irashobora kandi gukoreshwa ifatanije nindi miti igabanya ubukana nka SGLT2 inhibitor. SGLT2 ibuza glucose kumaraso muguteza glucose gusohora mu nkari. Guhuza byombi birashobora kurushaho kunoza igenzura ryamaraso glucose binyuze muburyo butandukanye kandi birashobora no kugira ingaruka zifatika mugucunga ibiro.
Uruhare rwa GLP-1 mugucunga ibiro
Kuribwa no kurya
GLP-1 ikora kuri reseptor ya GLP-1 muri sisitemu yo hagati yo hagati, cyane cyane muri hypothalamus. Hypothalamus n'akarere k'ingenzi mu mubiri kugenga ubushake bwo kurya no kuringaniza ingufu. Nyuma yo guhambira reseptor ya GLP-1 muri hypothalamus, GLP-1 irashobora kugenga irekurwa rya neuropeptide, nko kugabanya ururenda rwa neuropeptide Y (NPY), nikintu gikomeye gikurura ubushake bwo kurya. Byongeye kandi, GLP-1 irashobora kongera ibikorwa bya neuron ya proopiomelanocortin (POMC), ibikorwa byayo bitanga ibimenyetso byo guhaga. Binyuze muri ubwo buryo, GLP-1 irwanya ubushake bwo kurya, bigatuma abarwayi bagabanya ibiryo byabo. Mu bigeragezo by’amavuriro, abarwayi bafite umubyibuho ukabije cyangwa bafite ibiro byinshi bakoresheje GLP-1 bavuze ko ubushake bwo kurya bwagabanutse no gufata ibiryo, ibyo bikaba ari byo shingiro ryo kugabanya ibiro.
Kongera ingufu zikoreshwa
Usibye guhagarika ubushake bwo kurya, GLP-1 irashobora no guhindura imbaraga za metabolisme, kongera ingufu zikoreshwa. Ubushakashatsi bwerekana ko GLP-1 ishobora kongera ingufu zikoreshwa muguhuza ibikorwa bya tissue adipose. Ibibyimba bya adipose ni ubwoko bwihariye bwamavuta yibikorwa byibanze ni ugukoresha ingufu binyuze muri thermogenez. GLP-1 irashobora gukora inzira zimwe zerekana ibimenyetso mubice bya adipose yumukara, bigatera aside irike hamwe na thermogenez. Byongeye kandi, GLP-1 irashobora guhindura imbaraga za metabolism mumyanya nkimitsi, kongera ingufu zikoreshwa no kuruhuka. Kurugero, mubushakashatsi bwibikoko, nyuma yubuyobozi bwa GLP-1, ingufu za metabolisme zinyamanswa ziyongereye, kandi ibiro byumubiri byagabanutse nubwo gufata ibiryo byakomeje kuba bimwe, byerekana ko GLP-1 igira uruhare runini mugucunga ibiro byongera ingufu zikoreshwa.
Kugena ibinure bya metabolism
GLP-1 nayo igira ingaruka zoguhindura ibinure. Irashobora guteza imbere igabanuka ryibinure, kugabanya ibinure, no kubuza ibinure. Mu mwijima, GLP-1 irashobora guhagarika ibikorwa bya enzymes nka synthase ya fatty acide, bityo bikagabanya synthesis ya fatty. Byongeye kandi, muri tipusi ya adipose, GLP-1 irashobora guteza imbere kugabanuka kwamavuta, kongera irekurwa rya aside irike yubusa, kandi ikaborohereza kwinjira muri mitochondriya kugirango isenyuke, bityo kugabanya ububiko bwamavuta. Ubushakashatsi ku mavuriro bwerekanye ko nyuma yigihe cyo kuvura hamwe na GLP-1, ibinure by’umubiri by’abarwayi, cyane cyane ibinure by’imitsi, bigabanuka. Ibi ntabwo bifasha gusa kugabanya ibiro ahubwo binagira ingaruka zikomeye mugutezimbere syndrome de metabolike no kugabanya ibyago byindwara zifata umutima.
Gushyira mu bikorwa GLP-1 mu gucunga ibiro
Ku barwayi bafite umubyibuho ukabije cyangwa umubyibuho ukabije uherekejwe n'indwara zifitanye isano
GLP-1 ifite intego igaragara yabaturage yo gucunga ibiro. Ku barwayi bafite umubyibuho ukabije ufite BMI kg30 kg / m² cyangwa abarwayi bafite ibiro byinshi bafite BMI kg27 kg / m² kandi byibura imiterere imwe ijyanye nuburemere (nka hypertension, ubwoko bwa 2 metabolism, cyangwa hypercholesterolemia), niwo muti mwiza wo gucunga ibiro. Urukurikirane rwa STEP rwibizamini byamavuriro rwerekanye gutakaza ibiro kubarwayi bavuwe. Mu bushakashatsi bwa STEP 1, abarwayi bavuwe bageze ku kigereranyo cyo kugabanya ibiro hafi 15% mu byumweru 68, mugihe itsinda rya placebo ryatakaje hafi 2,4% gusa. Ibisubizo byerekana ko bishobora gufasha abarwayi bafite umubyibuho ukabije cyangwa umubyibuho ukabije bafite ibibazo bifitanye isano no kugabanya ibiro bikomeye kandi birambye, kuzamura umusaruro w’ubuzima, no kugabanya ibyago by’indwara ziterwa n'umubyibuho ukabije.
Ufatanije nubuzima bwimibereho
Mu gucunga ibiro, GLP-1 ikoreshwa muburyo bwo guhuza imibereho, harimo kugabanya gufata kalori no kongera imyitozo ngororamubiri. Niba kugabanya ibiro bishingiye gusa kumiti idahinduye ingeso zubuzima zitari nziza, ingaruka ntizihoraho. Guhuza ubwo buryo bwombi bigira ingaruka zifatika: imiti igabanya ubushake bwo kurya no kongera ingufu zikoreshwa, mugihe kugenzura imirire bigabanya gufata kalori no kongera imyitozo ngororamubiri byongera ingufu zikoreshwa, biganisha ku gutakaza ibiro cyane kandi birambye. Kurugero, mubikorwa bimwe byubuvuzi, abarwayi bakurikiza gahunda yimirire ya calorie nkeya yateguwe ninzobere mu mirire kandi bakongera igihe cyimyitozo ngororamubiri ya buri cyumweru mugihe cyo kwivuza bagera ku musaruro mwiza ugabanuka kuruta abishingikiriza gusa kumiti cyangwa kwivanga mubuzima. Ubu buryo bukomatanyije bushimangira akamaro ko gucunga neza mu gucunga ibiro, gufasha abarwayi gushyiraho ubuzima bwiza no kugera ku kugenzura igihe kirekire.
Umwanzuro
GLP-1 yerekana ubushobozi bukomeye haba kuvura metabolism no gucunga ibiro. Mu kuvura metabolism, igenzura neza glucose yamaraso ikoresheje uburyo bwinshi, igatezimbere imikorere ya selile, kandi irashobora gukoreshwa nka monotherapy cyangwa ifatanije nindi miti igabanya ubukana. Mu micungire y’ibiro, irwanya ubushake bwo kurya, ikongera ingufu zikoreshwa, kandi ikagenga metabolisme y’ibinure, bigatuma ibereye abarwayi bafite umubyibuho ukabije cyangwa ufite ibiro byinshi bafite ibibazo bifitanye isano. Iyo uhujwe nubuzima bwimibereho, bitanga ibisubizo byiza kurushaho.
Inkomoko
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Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
