MicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake

Pancreatic beta cell dysfunction 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 beta cell function remains largely elusive. In the current study, we identify the pathway by which miR-21 regulates glucose-stimulated insulin secretion utilizing mice lacking miR-21 in their beta cells (miR-21 beta KO). We find that miR-21 beta KO mice develop glucose intolerance due to impaired glucose-stimulated insulin secretion. Mechanistic studies reveal 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 results in rescue of the impaired glucose-stimulated insulin secretion. Furthermore, we demonstrate that delivery of miR-21 into the pancreas of type 2 diabetic db/db male mice is able to promote Glut2 expression and reduce blood glucose level. Taking together, our results reveal that miR-21 in islet beta cell promotes insulin secretion and support a role for miR-21 in the regulation of pancreatic beta cell function in type 2 diabetes. The microRNA miR-21 is induced in the islets of patients with glucose intolerance and diabetic mice. Here the authors report that deletion of miR-21 in pancreatic beta-cells impairs glucose-stimulated insulin secretion via reduced glucose uptake, while a miR-21 agomir reduces blood glucose leves in diabetic male mice.

Automated summary

In this study, researchers investigate the role of miR-21 in the regulation of pancreatic beta cell function. They find that miR-21 promotes glucose-stimulated insulin secretion by enhancing glucose uptake and up-regulating Glut2 expression. They also demonstrate that delivering miR-21 into the pancreas can decrease blood glucose levels in diabetic mice.