BCAS2 Participates in Insulin Synthesis and Secretion via mRNA Alternative Splicing in Mice.
Endocrinology
; 165(1)2023 Nov 20.
Article
in En
| MEDLINE
| ID: mdl-37820033
ABSTRACT
Insulin secreted by pancreatic ß cells is essential for maintaining blood glucose levels. Diabetes is caused primarily by a loss of ß cells or impairment of ß-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 ß 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-ßKO mice, and ß-cell mass and islet size were 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, 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-ßKO 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
/
Islets of Langerhans
/
Diabetes Mellitus, Type 2
/
Insulin-Secreting Cells
Limits:
Animals
Language:
En
Journal:
Endocrinology
Year:
2023
Document type:
Article
Affiliation country:
China