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1 kits (10 Vials)
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▎ Tsarin GLP-3
Source: PubChem |
Jeri: YA⊃1;QGTFTSDYSI-L⊃2;LDKK⁴AQA⊃1;AFIEYLLEGGPSSGAPPPS⊃3; Tsarin kwayoyin halitta: C 221H 342N 46O68 Nauyin Kwayoyin: 4731 g/mol Lambar CAS: 2381089-83-2 PubChem CID: 171390338 Saukewa: LY3437943 |
▎ GLP-3 Bincike
Menene asalin bincike na GLP-3?
Kiba yana daya daga cikin manyan matsalolin kiwon lafiyar jama'a a yau. Kiba na iya haifar da matsalolin kiwon lafiya iri-iri, kamar nau'in 2 na metabolism, cututtukan zuciya, hauhawar jini, dyslipidemia, da cututtukan hanta mai kitse mara-giya. Tare da ci gaba da karuwa a cikin abubuwan da ke faruwa na kiba, ana samun karuwar bukatar sababbin hanyoyin kwantar da hankali wanda zai iya sarrafa nauyin jiki yadda ya kamata da inganta yanayin kiwon lafiya [1] . Kodayake gyare-gyaren salon rayuwa, irin su ƙara yawan motsa jiki da rage cin abinci, su ne hanyoyin farko don sarrafa nauyin nauyi, tsawon lokaci na kula da asarar nauyi ya kasance kalubale ga yawancin manya da abin ya shafa. GLP-3 labari ne mai karɓar mai karɓa sau uku wanda ke aiki akan mai karɓar glucagon-kamar peptide-1 (GLP-1R), mai karɓar insulinotropic polypeptide mai dogaro da glucose (GIPR), da mai karɓar glucagon (GCGR). Wannan tsarin aikin mai karɓa da yawa yana ba shi fa'idodi na musamman a cikin asarar nauyi. Idan aka kwatanta da magungunan asarar nauyi waɗanda ke aiki akan mai karɓa ɗaya, GLP-3 na iya ƙarin daidaita tsarin tafiyar da rayuwa ta jiki [1] . GLP-3 yana samun asarar nauyi ta hanyar daidaita masu karɓar hormone da yawa. Ba wai kawai yana da tasiri mai mahimmanci na asarar nauyi ba amma har ma yana da ƙananan sakamako masu illa na gastrointestinal. Bugu da ƙari, idan aka kwatanta da wasu sababbin magungunan asarar nauyi, GLP-3, a matsayin mai agonist mai karɓa sau uku, yana da tasiri mai ƙarfi mai ƙarfi da kuma yawan adadin yawan jama'a.
Menene tsarin aikin GLP-3?
Tsarin aikin GLP-3 ya samo asali ne daga tasirin tasirinsa akan masu karɓa da yawa. Da farko, tasirinsa na agonist akan mai karɓa na glucagon-kamar peptide-1 (GLP-1R) yana ƙara haɓakar insulin, yana hana ƙwayar glucagon, yana rage matakan glucose na jini, kuma a lokaci guda yana jinkirta zubar da ciki, yana ƙaruwa, kuma yana rage cin abinci [2] . Abu na biyu, tasirinsa na agonist akan mai karɓar insulinotropic polypeptide mai karɓar glucose (GIPR) yana iya haɓaka haɓakar insulin, haɓaka amfani da glucose, kuma yana da tasiri akan metabolism na mai, hana lipolysis da haɓaka haɓakar mai [2] . Haka kuma, kodayake tasirin agonist na GLP-3 akan mai karɓar glucagon (GCGR) yawanci yana haɓaka glycogenolysis da gluconeogenesis a cikin hanta, yana haɓaka matakan glucose na jini, ƙarƙashin aikin GLP-3, wannan tasirin haɓakar glucose na jini yana raguwa ta sakamakon sauran masu karɓa guda biyu. A lokaci guda, yana inganta lipolysis kuma yana rage yawan kitse [2] . Wannan yanayin aiki mai yawan manufa na iya zama mafi inganci wajen magance kiba fiye da agonists masu karɓa ɗaya.
Ta hanyar kunna waɗannan masu karɓa guda uku a lokaci guda, GLP-3 na iya yin tasiri iri-iri na tsarin rayuwa da kuma haifar da tasirin warkewa akan kiba da cututtukan da ke da alaƙa. Dangane da daidaita matakan glucose na jini, saboda kunna GLP-1R da GIPR waɗanda ke haɓaka haɓakar insulin da hana haɓakar glucagon, da kunna GCGR ta hanyar tasirin sauran masu karɓa guda biyu, GLP-3 na iya daidaita matakan glucose na jini yadda ya kamata, wanda yake da matukar mahimmanci ga jiyya na nau'in 2, metabolism [1] . Dangane da rage yawan kitse, kunna GCGR yana inganta lipolysis kuma yana rage yawan kitse. A lokaci guda, kunna GLP-1R yana ƙara yawan jin daɗi kuma yana rage cin abinci, yana ƙara rage haɓakar mai [1, 2] . Bugu da ƙari, GLP-3 kuma yana da tasiri mai amfani akan cututtukan hanta maras-giya. Yana iya rage kitsen da ke cikin hanta da inganta aikin hanta. Wani bazuwar, makafi biyu, gwajin sarrafa wuribo ya nuna cewa matsakaicin canjin dangi a cikin kitsen hanta a cikin rukunin jiyya na GLP-3 a makonni 24 ya ragu sosai fiye da na rukunin placebo [3].
HbA1c, nauyin jiki, hawan jini, da lipids Bayanai sune mafi ƙanƙanta ma'anar murabba'i (tare da sandunan kuskure suna nuna SEs) daga saitin bincike na inganci, sai dai in an lura.
Source:PubMed [4]
Ta yaya daidai GLP-3 ke daidaita metabolism na glucose bayan kunna masu karɓar ukun?
GLP-3 yana sarrafa glucose na jini ta hanyoyi da yawa, gami da kunna GLP-1 da masu karɓa na GIP, haɓaka haɓakar insulin, hana ƙwayar glucagon, jinkirta zubar da ciki, daidaita metabolism mai, da rage matakan ANGPTL3/8. Dangane da tsarin glucose na jini, GLP-3 yana aiki akan GLP-1 da masu karɓar GIP, yana haɓaka haɓakar ƙwayoyin pancreatic β zuwa glucose, haɗawa da sakin insulin, sannan haɓaka haɓakawa da amfani da glucose ta kyallen takarda, cimma tasirin rage glucose na jini [4, 5] . (HbA1c), wanda galibi yana fa'ida daga rawar da yake takawa wajen haɓaka fitar insulin (Rosenstock J, 2023). A lokaci guda, kunna mai karɓar GLP-1 na iya hana ƙwayar glucagon ta ƙwayoyin α pancreatic, yana hana glucose jini daga girma. A cikin nazarin asibiti, an lura cewa matakan glucagon na marasa lafiya da ke amfani da GLP-3 sun ragu, wanda hakan yana taimakawa wajen tabbatar da kwanciyar hankali na glucose na jini [4, 5] . Kunna masu karɓar GLP-1 da GIP kuma na iya jinkirta adadin zubar da ciki, rage narkewar abinci da sha, da rage haɓakar hauhawar glucose na jini bayan cin abinci. Nazarin ya nuna cewa lokacin zubar da ciki na marasa lafiya da aka yi amfani da su tare da GLP-3 yana tsawaitawa sosai bayan cin abinci, don haka yana rage ƙimar ƙimar glucose na jini na postprandial [4].
Tsarin metabolism na mai ta GLP-3 shima yana shafar metabolism a kaikaice. Misali, a cikin nazarin marasa lafiya masu kiba, an gano cewa GLP-3 na iya rage matakan triglycerides (TG), low-density lipoprotein (LDL), da lipoprotein low-density (VLDL) cholesterol [2,6] . Wannan haɓakawa a cikin metabolism na lipid na iya kasancewa yana da alaƙa da haɓaka haɓakar insulin, ta haka yana ba da gudummawa ga sarrafa glucose na jini. Musamman, bayan GLP-3 jiyya, plasma 3-hydroxybutyric acid (3-HB) yana ƙaruwa, tare da karuwa a cikin 3-hydroxybutyrylcarnitine (C 4OH), rabon acetylcarnitine zuwa carnitine kyauta (C 2/ C 0), da kuma acylcarnitine matsakaici-sarkar, yana nuna haɓakar lipolysis a cikin ƙima a cikin ƙima da haɓakar kitse.
GLP-3 kuma zai iya rage jimlar dihydroceramides (DhCers), kuma wannan canji yana haɗuwa da ingantaccen haɓakar insulin, rage ciwon hanta, da kumburi na tsarin [6] . A lokaci guda, GLP-3 kuma zai iya rage ƙaddamar da hadaddun ANGPTL3 / 8 a cikin nau'in nau'in ciwon sukari na 2 na marasa lafiya, daidaita glucose metabolism [7] . ANGPTL3/8 shine mafi inganci mai hanawa na lipoprotein lipase (LPL), kuma matakin jininsa yana da alaƙa kai tsaye da TG da ƙananan ƙarancin lipoprotein cholesterol (LDL-C). GLP-3 yana rage matakin ANGPTL3/8, wanda zai iya daidaita glucose metabolism ta hanyar rage triglyceride mai arzikin lipoproteins [7] .
A wanne bangare GLP-3 ke nuna tasirin sa?
Muhimman tasirin asarar nauyi:
GLP-3 ya nuna gagarumin tasirin asarar nauyi a cikin gwaje-gwajen asibiti da yawa. Alal misali, a cikin binciken asibiti wanda ya shafi manya na 338 [2] , marasa lafiya da aka bi da su tare da nau'i daban-daban na GLP-3 sun sami asarar nauyi a cikin makonni 48. Daga cikin su, marasa lafiya a cikin rukunin kashi na 12mg suna da asarar nauyi na 24.2%, kuma yawancin marasa lafiya sun sami asarar nauyi zuwa digiri daban-daban. Misali, tsakanin marasa lafiya da ke karbar 4mg, 8mg, da 12mg allurai, 92%, 100%, da 100% na marasa lafiya sun rasa 5% ko fiye na nauyin jikinsu, bi da bi. A cikin wani binciken [8] , gwaje-gwajen da aka sarrafa guda biyu da suka shafi 353 nau'in 2 na marasa lafiya na metabolism sun nuna cewa idan aka kwatanta da placebo, GLP-3 zai iya rage nauyin jikin marasa lafiya ta 11.89kg kuma ya rage glycated haemoglobin (HbA1C). Bugu da ƙari, a cikin gwaji na marasa lafiya masu kiba marasa ciwon sukari, GLP-3 ya haifar da asarar nauyi na 24.2% a cikin marasa lafiya, kuma 83% na marasa lafiya sun rasa 15% ko fiye na nauyin jikinsu a makonni 48. Waɗannan sakamakon sun nuna cewa GLP-3 yana da babban yuwuwar asara mai nauyi.
Jiyya na nau'in 2 metabolism :
GLP-3 kuma yana nuna wasu yuwuwar a cikin jiyya na nau'in 2 metabolism. A wasu gwaje-gwajen asibiti, GLP-3 ya nuna raguwar haemoglobin glycated (HbA1c) da asarar nauyi mai dogaro da kashi. Alal misali, a cikin binciken daya, a cikin nau'in 2 na marasa lafiya na metabolism, GLP-3 ya nuna tasiri mai mahimmanci na sarrafa glucose na jini, yana rage glycated haemoglobin da 1.64% idan aka kwatanta da placebo [4, 8] . In addition, in a randomized, double-blind, placebo, and active-controlled parallel-group phase 2 trial, animal models with type 2 metabolism showed a significant reduction in glycated hemoglobin levels and a dose-dependent weight loss after receiving GLP-3 treatment [4] . Ana iya danganta wannan ga cikakken tasirin maganin akan GLP-1, GCGR, da GIPR, waɗanda ke haɓaka metabolism na glucose da ma'aunin kuzari.
Inganta abubuwan haɗari na zuciya:
GLP-3 ba zai iya rage nauyin jiki kawai ba har ma yana inganta abubuwan haɗari na zuciya da jijiyoyin jini, kamar bayanin martabar jini da matakan haemoglobin glycated. Wannan yana nuna kusancin pathophysiological tsakanin kiba da cututtukan zuciya, kuma GLP-3 na iya inganta lafiyar cututtukan zuciya na marasa lafiya masu kiba ta hanyoyi da yawa. Misali, rage marasa HDL-C, apoB, da LDLP matakan na iya rage haɗarin atherosclerosis; Rage matakan haemoglobin glycated na iya inganta sarrafa glucose na jini a cikin marasa lafiya na metabolism, ta haka rage haɗarin rikice-rikice na zuciya [8-10]. .
Maganin cutar hanta mai ƙiba mara-giya (NAFLD):
GLP-3 wani labari ne na peptide mai karɓar mai karɓa sau uku wanda ke hari ga mai karɓar glucagon (GCGR), mai karɓar insulinotropic polypeptide mai dogaro da glucose (GIPR), da mai karɓar glucagon-kamar peptide-1 (GLP-1R). Nazarin ya nuna cewa GLP-3 yana da yuwuwar a cikin maganin cututtukan hanta mara-giya. A cikin binciken daya, an gudanar da gwajin bazuwar, makafi biyu, gwajin sarrafa wuribo na tsawon makonni 48 akan mahalarta tare da cututtukan hanta mai rauni mai alaƙa da cututtukan hanta da abun ciki mai hanta na ≥10%. Sakamakon ya nuna cewa a cikin makonni 24, matsakaicin canje-canje a cikin kitsen hanta dangane da asali a cikin mahalarta da aka bi da su tare da nau'i-nau'i daban-daban na GLP-3 (1mg, 4mg, 8mg, da 12mg) sun kasance -42.9%, -57.0%, -81.4%, da -82.4%, bi da bi, yayin da a cikin rukunin placebo ya kasance + 3.3 % . Wannan yana nuna cewa GLP-3 na iya samun tasiri mai mahimmanci na warkewa akan cututtukan hanta mara-giya.
A ƙarshe, a matsayin sabon agonist mai karɓa sau uku, GLP-3 yana nuna babban yuwuwar maganin kiba da cututtukan da ke da alaƙa. Yana iya kunna mai karɓar glucagon, mai karɓar insulinotropic polypeptide mai dogaro da glucose, da mai karɓar glucagon-kamar peptide-1, yana daidaita tsarin metabolism na jiki gabaɗaya daga ma'auni masu yawa, inganta sarrafa glucose na jini, rage nauyin jiki, da daidaita metabolism na lipid. Bayyanar GLP-3 yana kawo sabbin zaɓuɓɓukan magani ga marasa lafiya masu kiba, nau'in metabolism na 2, da sauran cututtuka. Ana sa ran za a karya ta hanyar iyakokin magungunan magungunan masu karɓa guda ɗaya na gargajiya, samar da makami mafi ƙarfi don magance matsalolin matsalolin kiba da cututtuka na rayuwa, inganta ci gaba da ci gaban filayen kiwon lafiya masu dangantaka, inganta rayuwar marasa lafiya, da rage nauyin kiwon lafiya na zamantakewa.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Rosenstock J kwararre ne mai matukar tasiri a fannin likitanci, yana hada gwiwa da cibiyoyi kamar Jami'ar Texas Southwestern Medical Center da Jami'ar Texas Dallas. Hakanan yana gudanar da bincike a cibiyoyi kamar Cibiyar VIGOR ta Kanada da Veloc Clin Res Ctr Med City. Bincikensa ya shafi ilimin endocrinology da metabolism, tsarin zuciya da jijiyoyin jini da ilimin zuciya, ilimin harhada magunguna, da magungunan gwaji, tare da mai da hankali kan metabolism, kiba, da jiyya masu alaƙa da haɓakar ƙwayoyi. J Rosenstock ya sami nasara mai mahimmanci a cikin maganin asibiti, ana kiransa mai suna Mai Bincike Mai Girma daga 2017 zuwa 2024. Wannan yana nuna babban tasiri da kuma fahimtar aikinsa. Ta hanyar haɗin gwiwa tare da cibiyoyin bincike da yawa, ya sami nasarar fassara sakamakon bincike na asali a cikin aikace-aikacen asibiti, yana amfanar marasa lafiya da cututtuka na rayuwa da na zuciya da jijiyoyin jini da kuma ci gaban kimiyyar likita. An jera Rosenstock J a cikin ambaton ambaton [4].
