Dysregulation of microRNA(miRNA)expression following the development of obesity is closely linked to the onset of type 2 diabetes mellitus(T2DM).Identifying differentially expressed miRNAs and their roles in regulatin...Dysregulation of microRNA(miRNA)expression following the development of obesity is closely linked to the onset of type 2 diabetes mellitus(T2DM).Identifying differentially expressed miRNAs and their roles in regulating glucose metabolism will provide a theoretical foundation for the molecular mechanisms underlying obesity-induced T2DM.Here,we perform a genome-wide association study involving 5 glycolipid metabolism traits in 1783 Kazakh and 1198 Uyghur individuals to identify miRNAs associated with fasting plasma glucose(FPG)levels.A miR-548ab mimic and inhibitor are administered to hepatocytes and adipocytes,as well as obese and diabetic mice,to determine miR-548ab-related downstream signalling pathways.The effects of miR-548ab on glucose metabolism are validated using the glucose tolerance test and insulin tolerance test.Collectively,these results indicate that miR-548ab is significantly associated with FPG levels and obesity-related T2DM in both Kazakh and Uyghur populations.The miR-548ab-GULP1/SLC25A21-GLUT4 network exerts regulatory effects on glucose metabolism,obesity,and T2DM,positioning it as a candidate risk factor,potential diagnostic marker,and therapeutic target for obesity-induced T2DM.Additionally,through evolutionary analysis,the authentic variants or haplotypes of GULP1 and SLC25A21 are categorized according to their genetic susceptibility to T2DM.The miR-548ab inhibitor shows beneficial effects in obese and diabetic mice.展开更多
基金supported by the Natural Science Foundation of China(82160156,82260162,and 32370669)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38040200)+1 种基金the Tianshan Talent Project in Xinjiang Autonomous Region(2023TSYCCX0116 and 2023TSYCQNTJ0032)the Scientific and Technological Research Project of Xinjiang Production and Construction Corps(2022ZD001,2021AB028,2022AB022,2023AB057,and 2023ZD037).
文摘Dysregulation of microRNA(miRNA)expression following the development of obesity is closely linked to the onset of type 2 diabetes mellitus(T2DM).Identifying differentially expressed miRNAs and their roles in regulating glucose metabolism will provide a theoretical foundation for the molecular mechanisms underlying obesity-induced T2DM.Here,we perform a genome-wide association study involving 5 glycolipid metabolism traits in 1783 Kazakh and 1198 Uyghur individuals to identify miRNAs associated with fasting plasma glucose(FPG)levels.A miR-548ab mimic and inhibitor are administered to hepatocytes and adipocytes,as well as obese and diabetic mice,to determine miR-548ab-related downstream signalling pathways.The effects of miR-548ab on glucose metabolism are validated using the glucose tolerance test and insulin tolerance test.Collectively,these results indicate that miR-548ab is significantly associated with FPG levels and obesity-related T2DM in both Kazakh and Uyghur populations.The miR-548ab-GULP1/SLC25A21-GLUT4 network exerts regulatory effects on glucose metabolism,obesity,and T2DM,positioning it as a candidate risk factor,potential diagnostic marker,and therapeutic target for obesity-induced T2DM.Additionally,through evolutionary analysis,the authentic variants or haplotypes of GULP1 and SLC25A21 are categorized according to their genetic susceptibility to T2DM.The miR-548ab inhibitor shows beneficial effects in obese and diabetic mice.
