The Role Of LAMTOR1 In Islet ? Cell Insulin Secretion

Purpose: This study investigated the role and molecular mechanism of LAMTOR1 in islet beta cell function.Method: A mouse model of LAMTOR1 islet specific knockout(?-LAMTOR1-KO)was constructed in the context of C57 mice,and knockdown of mouse islet LAMTOR1 gene was verified by Western blotting.The ?-cell function of mice was evaluated by intraperitoneal glucose tolerance test and hyperglycemic clamp test in vivo.Islet perfusion,mitochondrial functional analyses and Western blotting were performed to investigate the individual steps in the insulin secretion pathway.Result: Compared with the control mice,the glucose tolerance test showed that the glucose level of the ?-LAMTOR1-KO group was lower,and the insulin secretion level of the ?-LAMTOR1-KO group was significantly increased during the hyperglycemic clamp and islet perfusion experiments.Mitochondrial dysfunction of mouse islet cells in the ?-LAMTOR1-KO group,but deletion of LAMTOR1 increased glutamate content in insulin particles and acetyl-CoA carboxylase 1(ACC1)activity,eventually leading to ?-cells Glucose-stimulated insulin secretion is increased.Conclusion: LAMTOR1 is important for maintaining mitochondrial function of pancreatic beta cells.Although the lack of LAMTOR1 impairs islet beta cell mitochondrial function leading to impaired triggering pathways for insulin secretion.However,the amplification pathways caused by increased glutamate and ACC1 metabolism compensate for the defects of the trigger pathway and ultimately lead to an increase in glucose-stimulated insulin secretion.