BCAS2 participates in insulin synthesis and secretion via mRNA alternative splicing in mice.

Insulin secreted by pancreatic β cells is essential for maintaining the level of blood glucose. Diabetes is caused primarily by loss of β cells or impairment of β cell function. A previous whole-transcriptome analysis of islets from a type 2 diabetes (T2D) group and a control group showed that splicing disorder occurred in approximately 25% of splicing events. Breast carcinoma amplified sequence 2 (BCAS2) is a spliceosome component whose function in islet β 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-βKO mice, and β cell mass and islet size were analyzed by immunohistochemistry. Glucose intolerance developed in Bcas2 f/f-βKO mice, but there were no significant differences in pancreas weight, insulin sensitivity, β cell mass or islet size. Furthermore, observation of glucose-stimulated insulin secretion (GSIS) 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-βKO 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.