By Cocer Peptides 
kwanaki 18 da suka gabata
DUKKANIN LABARI DA BAYANIN KYAUTATAWA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da duk wani yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
Bayani na Triple Agonists
A cikin 'yan shekarun nan, tare da zurfafa bincike a cikin pathogenesis na cututtuka na rayuwa, haɓakar magungunan agonist masu yawa da ke da alaka da masu karɓar hormone da yawa ya zama batu mai zafi. Retatrutid labari ne mai sau uku agonist na masu karɓar insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), da masu karɓar glucagon (GC).
(1) Tushen Jiki na Ayyukan Mai karɓar Hormone
Mai karɓar GIP: GIP shine hormone mai ɓoye insulin na hanji wanda ƙwayoyin K ke ɓoye a cikin ƙananan hanji, wanda aka saki da sauri bayan abinci. Bayan ɗaure ga mai karɓa na GIP, GIP yana ƙarfafa ƙwayar insulin, kuma wannan sakamako mai ban sha'awa yana dogara ne akan glucose, ma'ana cewa yayin da matakan glucose na jini ya tashi, GIP yana haɓaka tasirin ɓoyewar insulin, yana taimakawa wajen kiyaye matakan glucose na jini. Bugu da ƙari, GIP yana shiga cikin ƙa'idar metabolism na lipid, yana tasiri bambance-bambancen adipocyte da tarin lipid.
Hoto 1. Maganin RETA ko SEMA yana rage nauyin jiki kuma yana inganta glucose na jini mai azumi. An ba da rahoton canje-canje na kashi bisa dari na nauyin jiki daga asali. b, Epididymal farin adipose nama nauyi an ƙididdige shi a ƙarshen ƙarshen. c An ƙididdige glucose na jini mai azumi a asali kuma a duk tsawon binciken a wuraren da aka nuna har zuwa ƙarshen ƙarshen. d An ba da rahoto game da haɓakar ƙwayar cuta ko 'ƙarin kai'.
Mai karɓar GLP-1: GLP-1 yana ɓoye ta ƙwayoyin L na hanji kuma yana da tasirin insulinotropic mai dogaro da glucose, yana haɓaka haɓakar insulin da sakin jiki, yana hana ɓoyayyun glucagon, da rage fitowar glucose na hanta. GLP-1 kuma yana jinkirta zubar da ciki, yana ƙara koshi, kuma ta haka yana rage yawan abinci. Yana da tasiri mai kariya da haɓakawa akan ƙwayoyin beta na pancreatic, yana taimakawa wajen kula da aikin pancreatic.
3. Mai karɓar GC:
Bayan ɗaure ga mai karɓar GC, glucagon da farko yana aiki akan hanta ta hanyar haɓaka glycogenolysis da gluconeogenesis, ta haka yana haɓaka matakan glucose na jini. A cikin metabolism na lipid, yana haɓaka lipolysis, yana haɓaka sakin da iskar shaka na fatty acid don kuzari. A ƙarƙashin yanayin ilimin lissafi na al'ada, ana hana fitowar glucagon lokacin da matakan glucose na jini ya tashi don kiyaye ma'aunin glucose.
(2) Amfanin Ayyukan Agonist Uku
A matsayin mai agonist sau uku, Retatrutid na iya kunna waɗannan masu karɓa guda uku a lokaci guda, yana yin tasirin aiki tare. Ta hanyar kunna masu karɓar GIP da GLP-1, yana haɓaka haɓakar insulin mai dogaro da glucose, yana rage yawan matakan glucose na jini yadda ya kamata. Ƙara yawan gamsuwa da jinkirin zubar da ciki da aka haifar ta hanyar kunna mai karɓar GLP-1, tare da lipolysis da aka inganta ta hanyar kunna mai karɓar GC, tare da ba da gudummawa ga sarrafa nauyi. Wannan nau'in aikin da aka yi niyya da yawa yana ba da ƙarin ƙayyadaddun ƙa'idodi na hanyoyin tafiyar matakai daban-daban na pathophysiological waɗanda ke da alaƙa da cututtukan rayuwa.
Hanyar Ayyukan Retatrutid a cikin Cututtukan Metabolic
Cututtukan ƙwayar cuta nau'in yanayi ne wanda ke haifar da rushewa a cikin hanyoyin rayuwa a cikin jiki, gami da yanayi na yau da kullun kamar su ciwon sukari, kiba, da cututtukan hanta mai ƙiba. Retatrutid yana aiwatar da tasirin sa akan waɗannan cututtukan rayuwa ta hanyar abubuwan agonist guda uku na musamman.
(1) Tsarin Aiki a Ciwon Suga
Tsarin Glucose: Retatrutid yana kunna masu karɓar GIP da GLP-1, yana haɓaka haɓakar insulin-dogara na glucose. Lokacin da matakan glucose na jini ya tashi, yana da kyau yana motsa ƙwayoyin beta na pancreatic don ɓoye insulin, yana haɓaka ɗaukar glucose da amfani, ta haka yana rage matakan glucose na jini. Ta hanyar hana fitowar glucagon da rage fitowar glucose na hanta, yana ƙara daidaita matakan glucose na jini. A cikin gwaje-gwajen asibiti da suka shafi marasa lafiya da nau'in ciwon sukari na 2, magani na Retatrutid ya haifar da raguwa mai yawa a cikin matakan glucose na azumi da na gaba.
Kariyar ƙwayoyin beta na pancreatic: Kunna mai karɓar GLP-1 ba wai kawai yana haɓaka fitar insulin ba amma yana da tasiri mai kariya da haɓakawa akan ƙwayoyin beta na pancreatic. Retatrutid na iya cimma wannan ta hanyar ci gaba da kunna mai karɓar GLP-1, rage jinkirin apoptosis na ƙwayoyin beta, haɓaka adadinsu da aikinsu, ta haka inganta ƙarfin ɓoye insulin da kiyaye matakan glucose na jini na dogon lokaci.
(2) Hanyar aiki a cikin kiba
Ka'idojin amfani da makamashi: Retatrutid yana kunna masu karɓar GLP-1, jinkirta zubar da ciki, tsawaita lokacin riƙe abinci a cikin ciki, haɓaka satiety, da rage cin abinci. Zai iya yin aiki a kan tsarin kulawa na tsakiya don daidaita abubuwan da ke da alaka da ci, irin su hana sakin orexin, da rage yawan ci, kuma ta haka ne sarrafa yawan kuzari.
Ƙarfafa Kudaden Makamashi: Kunna mai karɓar GC yana haɓaka lipolysis, ƙara sakin da iskar shaka na fatty acid don samar da makamashi. Rashin iskar shaka na fatty acid yana ba da kuzari ga jiki, yana rage ajiyar mai, kuma yana taimakawa rage nauyi. Kunna mai karɓar GIP kuma yana shiga cikin ka'idojin metabolism na makamashi, yana ƙara yawan kashe kuzari.
Hoto 2 Maganin RETA yana rage nauyin jiki da adiposity, yana inganta glucose na jini mai azumi. An ba da rahoton canje-canjen kashi bisa ɗari na nauyin jiki daga tushe. b Epididymal farin adipose nama an auna shi a ƙarshen ƙarshen kuma an daidaita shi zuwa jimlar nauyin jiki. c An ƙididdige glucose na jini mai azumi a asali kuma a duk tsawon binciken a wuraren da aka nuna har zuwa ƙarshen ƙarshen.
(3) Hanyar aiki a cikin cututtukan hanta mai kitse mara-giya
Ingantacciyar ƙwayar cuta ta hanta: Retatrutid yana kunna mai karɓar GC, yana haɓaka raguwa da β-oxidation na mai a cikin hanta, ta haka yana rage tarin mai a cikin hanta. Kunna masu karɓa na GIP da GLP-1 na iya daidaita maganganun kwayoyin halittar da ke da alaƙa da metabolism na lipid a cikin hanta, haɓaka maganganun masu jigilar fatty acid da fatty acid oxidases, ta haka inganta haɓakar fatty acid da oxidation, da haɓaka haɓakar hanta.
Ingantacciyar fahimtar insulin: Yayin haɓaka tsarin glucose da haɓaka haɓakar insulin, Retatrutid na iya haɓaka haɓakar insulin hanta ta hanyar kunna masu karɓar GLP-1. Ingantacciyar fahimtar insulin yana haɓaka martanin hanta ga insulin, mafi kyawun hana fitowar glucose na hanta, rage haɓakar fatty acid de novo, kuma ta haka yana rage steatosis na hanta.
Aikace-aikace da Tasirin Retatrutid a cikin Cututtukan Metabolic
(1) Aikace-aikace a cikin Ciwon sukari
Effects Control lycemic: Retatrutid yana nuna mahimman tasirin sarrafa glycemic a cikin marasa lafiya da nau'in ciwon sukari na 2. Bisa ga bayanai, marasa lafiya da aka yi wa Retatrutid sun nuna raguwa mai yawa a matakan haemoglobin A1c (HbA1c). A cikin gwajin da aka bazu wanda ya ƙunshi marasa lafiya 353 da nau'in ciwon sukari na 2, matakan HbA1c a cikin rukunin jiyya na Retatrutid sun ragu da 1.64% daga asali, yayin da babu wani canji mai mahimmanci a cikin rukunin placebo.
Kwatanta da Sauran Magunguna: Idan aka kwatanta da magungunan antidiabetic na gargajiya irin su metformin ko GLP-1 agonists masu karɓa, Retatrutid yana nuna ingantaccen tasirin sarrafa glucose na jini.
(2) Aikace-aikace a cikin kiba
Sakamakon asarar nauyi: Retatrutid yana nuna tasiri mai mahimmanci a cikin maganin kiba. A cikin gwaje-gwajen asibiti da aka yi niyya ga manya masu kiba, an lura da asarar nauyi sosai bayan makonni 48 na jiyya tare da allurai daban-daban na Retatrutid. A cikin gwaji guda ɗaya, marasa lafiya da aka bi da su tare da kashi na 12mg na Retatrutid sun sami matsakaicin asarar nauyi na 24.2% bayan makonni 48, idan aka kwatanta da kawai 2.1% a cikin rukunin placebo. Bugu da ƙari, 83% na mahalarta cikin ƙungiyar masu yawan adadin sun sami asarar nauyi na 15% ko fiye, wanda ya zarce ƙimar 2% a cikin rukunin placebo.
Tasirin Tsawon Lokaci: Retatrutid yana kula da tasirin asarar nauyi da kyau a duk lokacin jiyya. Wannan yana nuna cewa yin amfani da dogon lokaci zai iya taimakawa wajen kiyaye nauyin da ya dace da kuma hana sake dawowa, wanda ke da amfani ga kula da kiba na dogon lokaci.
(3) Aikace-aikace a cikin cututtukan hanta mai kitse mara-giya
Rage kitsen hanta: A cikin marasa lafiya da ke fama da cututtukan hanta da ke da alaƙa da cututtukan hanta da kitsen hanta ≥10%, jiyya na Retatrutid ya haifar da raguwar kitsen hanta. A cikin bazuwar, makafi biyu, gwajin sarrafa wuribo, a cikin makonni 24, abun ciki mai hanta ya ragu da 81.4% da 82.4% daga asali a cikin 8 MG da 12 MG na ƙungiyoyi, bi da bi, yayin da ƙungiyar placebo ta karu da kawai 0.3%.
Abũbuwan amfãni da Yiwuwar Agonist Uku
Retatrutid gabaɗaya yana daidaita hanyoyin pathophysiological da yawa na cututtukan rayuwa ta hanyar kunna GIP, GLP-1, da masu karɓar GC lokaci guda. Daga sarrafa glucose na jini, sarrafa nauyi, don haɓaka haɓakar hanta na hanta, wannan tsarin aiki mai niyya da yawa yana ba da cikakkiyar gyare-gyare na rikice-rikice na rayuwa idan aka kwatanta da magungunan da aka yi niyya guda ɗaya, yana nuna yuwuwar magance hadadden etiology na cututtukan rayuwa. Bayanan gwaji na asibiti na yanzu sun nuna cewa Retatrutid ya sami sakamako mai mahimmanci a cikin maganin cututtuka na rayuwa irin su ciwon sukari, kiba, da cututtukan hanta mai ƙiba.
Kammalawa
A matsayin sabon agonist sau uku, Retatrutid yana ɗaukar alƙawari don maganin cututtukan rayuwa.
Sources
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[4] Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutid don Kiba - Gwajin Mataki na 2 [J]. New England Journal of Medicine, 2023,389 (6): 514-526.DOI: 10.1056/NEJMoa2301972.
[5] Doggrell SA. Shin retatrutide (LY3437943), GLP-1, GIP, da agonist mai karɓar glucagon mataki ne na gaba a cikin maganin ciwon sukari da kiba?[J]. Ra'ayin Kwararru Akan Magungunan Bincike, 2023,32(5):355-359.DOI:10.1080/13543784.2023.2206560.
Samfura akwai don amfani da bincike kawai:
