| First Author | Chen X | Year | 2023 |
| Journal | Endocrinology | Volume | 165 |
| Issue | 1 | PubMed ID | 37820033 |
| Mgi Jnum | J:343520 | Mgi Id | MGI:7565925 |
| Doi | 10.1210/endocr/bqad152 | Citation | Chen X, et al. (2023) BCAS2 Participates in Insulin Synthesis and Secretion via mRNA Alternative Splicing in Mice. Endocrinology 165(1) |
| abstractText | 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-betaKO mice, and beta-cell mass and islet size were analyzed by immunohistochemistry. Glucose intolerance developed in Bcas2 f/f-betaKO 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-betaKO 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. |
