GSE191194
MicroRNA-21 Promotes Pancreatic ß cell Function through Modulating Glucose Uptake
Pancreatic ß cell dysfunction greatly contributes to the pathogenesis of type 2 diabetes. MiR-21 has been shown to be induced in the islets of glucose intolerant patients and type 2 diabetic mice. However, the role of miR-21 in the regulation of pancreatic ß cell function remains largely elusive. In the current study, we studied the pathway by which miR-21 regulates glucose-stimulated insulin secretion utilizing mice lacking miR-21 in their ß cells (miR-21ßKO). We found that miR-21ßKO mice developed glucose intolerance due to impaired glucose-stimulated insulin secretion. Mechanistic studies revealed that miR-21 enhances glucose uptake and subsequently promotes insulin secretion by up-regulating Glut2 expression in a miR-21-Pdcd4-AP-1 dependent pathway. Over-expression of Glut2 in knockout islets resulted in rescue of the impaired glucose-stimulated insulin secretion. Furthermore, we demonstrated that delivery of miR-21 into the pancreas of type 2 diabetic db/db mice is able to promote Glut2 expression and significantly reduce blood glucose level. Taking together, our results reveal that miR-21 in islet ß cell promotes insulin secretion and support a role for miR-21 in the adaptation of pancreatic ß cell function in type 2 diabetes. Overall design: Examination  RNA expression  in WT&miR-21ßKO  islet