BCAS2 Participates in Insulin Synthesis and Secretion via mRNA Alternative Splicing in Mice

Insulin secreted by pancreatic beta cells is essential for maintaining blood glucose levels. Diabetes is caused primarily by a loss of beta cells or impairment of beta-cell function. A previous whole-transcriptome analysis of islets from a type 2 diabetes group and a control group showed that a splicing disorder occurred in approximately 25% of splicing events. Breast carcinoma amplified sequence 2 (BCAS2) is a spliceosome component whose function in islet beta cells is unclear. Here, we report that knockdown of Bcas2 decreased glucose- and KCl-stimulated insulin secretion in the NIT-1 cell line. Pancreas weight, glucose tolerance, and insulin sensitivity were measured in normal chow-fed Bcas2 f/f-beta KO mice, and beta-cell mass and islet size were analyzed by immunohistochemistry. Glucose intolerance developed in Bcas2 f/f-beta KO mice, but there were no significant differences in pancreas weight, insulin sensitivity, beta-cell mass, or islet size. Furthermore, observation of glucose-stimulated insulin secretion and insulin secretion granules in normal chow-fed mice revealed that the insulin level in serum and the number of insulin secretion granules were decreased in Bcas2 f/f-beta KO mice. These differences were related to 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.