By Cocer Peptides 
kwanaki 18 da suka gabata
DUKKANIN LABARI DA BAYANIN KAYAYYA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Samfuran da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don bincike na 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 kowane 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 aka yi niyya ga masu karɓar hormone da yawa ya zama batu mai zafi. GLP-3 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 na azumi. An ba da rahoton canje-canje na kashi dari na nauyin jiki daga asali. b, Epididymal farin adipose nama nauyi an ƙididdige shi a wurin ƙarshe. 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 rahoton ƙaddamar da ƙwayar cuta ko 'ƙarin ci gaba'.
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 fitar da 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 inganta lipolysis, yana haɓaka sakin da iskar shaka na fatty acid don makamashi. 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 agonist sau uku, GLP-3 na iya kunna waɗannan masu karɓa guda uku a lokaci guda, suna yin tasirin daidaitawa. 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 pathophysiological daban-daban waɗanda ke da alaƙa da cututtukan rayuwa.
Hanyar Ayyukan GLP-3 a cikin Cututtukan Metabolic
Cututtukan ƙwayar cuta wani nau'in yanayi ne wanda ke haifar da rushewa a cikin tafiyar matakai na rayuwa a cikin jiki, gami da yanayi na yau da kullun kamar metabolism, kiba, da cututtukan hanta mai ƙiba mara-giya. GLP-3 yana aiwatar da tasirin sa akan waɗannan cututtukan rayuwa ta hanyar keɓancewar abubuwan agonist guda uku.
(1) Tsarin Aiki a Ciwon Suga
Tsarin Glucose: GLP-3 yana kunna GIP da masu karɓar GLP-1, yana haɓaka haɓakar insulin-dogara da glucose. Lokacin da matakan glucose na jini ya tashi, ya fi dacewa 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 yawan fitowar glucose na hanta, yana ƙara daidaita matakan glucose na jini. A cikin gwaje-gwajen asibiti da suka shafi marasa lafiya tare da nau'in metabolism na nau'in 2, jiyya na GLP-3 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. GLP-3 na iya cimma wannan ta hanyar ci gaba da kunna mai karɓar GLP-1, rage jinkirin beta apoptosis, ƙara 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: GLP-3 yana kunna masu karɓar GLP-1, yana jinkirta zubar da ciki, tsawaita lokacin riƙe abinci a cikin ciki, haɓaka koshi, da rage cin abinci. Yana iya yin aiki a kan tsarin kulawa na tsakiya don daidaita abubuwan da ke da alaka da ci, irin su hana sakin orexin, ƙara rage 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 makamashi ga jiki, yana rage ajiyar mai, kuma yana taimakawa wajen asarar 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-canje na kashi dari a cikin nauyin jiki daga asali. 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: GLP-3 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 karɓar 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, don haka haɓaka haɓakar fatty acid da iskar oxygen, da haɓaka haɓakar hanta.
Ingantacciyar fahimtar insulin: Yayin haɓaka tsarin glucose da haɓaka haɓakar insulin, GLP-3 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 kawar da steatosis na hanta.
Aikace-aikace da Tasirin GLP-3 a cikin Cututtukan Metabolic
(1) Aikace-aikace a cikin Ciwon sukari
Effects Control lycemic: GLP-3 yana nuna mahimman tasirin sarrafa glycemic a cikin marasa lafiya tare da nau'in metabolism na 2. Bisa ga bayanai, marasa lafiya da aka yi wa GLP-3 sun nuna raguwa mai yawa a cikin matakan haemoglobin A1c (HbA1c). A cikin gwajin da aka bazu wanda ya ƙunshi marasa lafiya 353 tare da nau'in 2 na metabolism, matakan HbA1c a cikin rukunin jiyya na GLP-3 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, GLP-3 yana nuna ingantaccen tasirin sarrafa glucose na jini.
(2) Aikace-aikace a cikin kiba
Sakamakon asarar nauyi: GLP-3 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 mai yawa bayan makonni 48 na jiyya tare da allurai daban-daban na GLP-3. A cikin gwaji ɗaya, marasa lafiya da aka bi da su tare da kashi 12mg na GLP-3 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: GLP-3 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 kula da nauyin nauyi 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 rashin aiki na rayuwa mai alaƙa da cututtukan hanta mai hanta da abun ciki mai hanta ≥10%, jiyya na GLP-3 ya haifar da raguwar yawan 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
GLP-3 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 lipid metabolism, wannan tsarin aiki mai niyya da yawa yana ba da cikakkiyar gyara ga rikice-rikice na rayuwa idan aka kwatanta da magungunan da aka yi niyya guda ɗaya, yana nuna yuwuwar magance hadaddun etiology na cututtukan rayuwa. Bayanan gwaji na asibiti na yanzu sun nuna cewa GLP-3 ya sami sakamako mai mahimmanci a cikin maganin cututtuka na rayuwa kamar metabolism, kiba, da cututtukan hanta maras barasa.
Kammalawa
A matsayin sabon agonist sau uku, GLP-3 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 GLP-3 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 GLP-3 (LY3437943), GLP-1, GIP, da glucagon agonist mai karɓar glucagon mataki ne na gaba a cikin maganin metabolism 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:
