MicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake.
Ruiling LiuCuilian LiuXiaozhen HePeng SunBin ZhangHaoran YangWeiyun ShiQingguo RuanPublished in: Nature communications (2022)
Pancreatic β 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 β 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 β cells (miR-21βKO). We find that miR-21βKO 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 β cell promotes insulin secretion and support a role for miR-21 in the regulation of pancreatic β cell function in type 2 diabetes.
Keyphrases
- cell proliferation
- long non coding rna
- blood glucose
- long noncoding rna
- type diabetes
- poor prognosis
- single cell
- oxidative stress
- chronic kidney disease
- insulin resistance
- adipose tissue
- induced apoptosis
- bone marrow
- end stage renal disease
- prognostic factors
- mesenchymal stem cells
- skeletal muscle
- cell cycle arrest
- patient reported