BCAS2 is involved in insulin synthesis and secretion by mRNA alternative splicing

Insulin secreted by pancreatic ß cells is essential for maintaining the level of blood glucose. Diabetes is mainly caused by the loss of ß cells or impaired ß cell function. The previous study performed a whole transcriptome analysis on the islets of T2D and the control group, and the results showed that the splicing disorder of the splicing event was about 25%, breast carcinoma amplified sequence 2(BCAS2) is one of the components of the spliceosome, and its function in islet ß cell is unclear. Here we report that knockdown of Bcas2 decreases in glucose and KCl-stimulated insulin secretion in the NIT-1 cell line. The pancreas weight, glucose tolerance and insulin sensitivity were detected in normal chow-fed and high-fat diet-fed Bcas2 f/f-ßKO mice, and ß cell mass and islet size was analyzed by immunohistochemistry. Glucose intolerance developed in Bcas2 f/f-ßKO mice, but there were no significant differences in pancreas weight, insulin sensitivity, ß cell mass and islet size. Further, GSIS and observation of insulin secretion granules were performed on normal chow-fed mice, and it was found that the insulin level in serum decreased and the number of insulin secretion granules decreased in Bcas2 f/f-ßKO mice, which was related to the abnormal splicing of Syt7 and Tcf7l2 pre-mRNA. Taken together, these results demonstrate that BCAS2 is involved in alternative splicing during insulin synthesis and secretion. Elisa,islet isolation,insulin secretion Overall design: Knockdown of Bcas2 in ß cells and control ß cells.