Study The Role Of TRPA1 And Cav1.2 In FXR-Mediated RYGB-Potentiated Insulin Secretion In Pancreatic B Cells

The main cause of type 2 diabetes is the relative lack of insulin secretion,so it has great significance to study the process and mechanism of insulin secretion.Insulin secretion is precise and complex regulatory process in vivo.Glucose that transport to cell through transporter GLUT2 is the main inducer for insulin secretion,it can produce ATP by metabolism and increase the ratio of ATP/ADP,then close the KATP channel of ATP sensitive.The closure of the potassium channel causes cell depolarization and open the calcium channel,then Ca2+ influx increase intracellular Ca2+ concentration,promote insulin secretion in pancreatic beta cells.Glucose-stimulated insulin secretion in pancreatic beta cell is a series of processes and intracellular calcium concentration plays an important role in this process.Calcium concentration is directly related to calcium channel,so it is very important to study the changes of calcium channel in the disorder of insulin secretion.Clinical and basic studies have found that Roux-en-Y gastric bypass(RYGB)can significantly improve the symptoms of hyperglycemia in type 2 diabetes.We also found that RYGB can increase insulin secretion and FXR(farnesoid X receptor)expression.As a kind of bile acid receptor,FXR has been found to play a key role in the regulation of glucose metabolism.In this paper,glucose-induced action potential and membrane potential were recorded by whole-cell electrophysiology,and the size of calcium current on islet B cells was studied.The expression of calcium channel and TRPA1 channel in m RNA and protein were detected by Q-PCR and western blot.ELASA technique was used to detect the insulin secretion of INS-1cell line and pancreatic islet under glucose stimulation.Through these experimental techniques,we has obtained the following results:(1)FXR can influence the glucose-stimulated insulin secretion through regulating the level of TRPA1 channel transcription in islet B cells;(2)FXR can raise the glucose-stimulated insulin secretion through regulating the level of calcium channel transcription and increasing calcium currents in islet B cells.These results in this paper can help people understand the FXR mediatedregulatory mechanism of insulin secretion in pancreatic beta-cell after RYGB and provide new therapeutic targets for the treatment of diabetes.