[HTML][HTML] MicroRNA-7a regulates pancreatic β cell function

M Latreille, J Hausser, I Stützer… - The Journal of …, 2014 - Am Soc Clin Investig
M Latreille, J Hausser, I Stützer, Q Zhang, B Hastoy, S Gargani, J Kerr-Conte, F Pattou
The Journal of clinical investigation, 2014Am Soc Clin Investig
Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following
pathological stress and are the underlying cause of several disease conditions. In
pancreatic β cells, miRNAs have been largely unstudied and little is known about how
specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the
adaptation of β cell function to metabolic stress. In this study, we determined that miR-7 is a
negative regulator of GSIS in β cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 …
Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic β cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of β cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in β cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates β cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in β cells developed diabetes due to impaired insulin secretion and β cell dedifferentiation. Interestingly, perturbation of miR-7a expression in β cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine β cell mass. Furthermore, we found that miR-7a levels are decreased in obese/diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated β cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic β cells and support a role for miR-7 in the adaptation of pancreatic β cell function in obesity and type 2 diabetes.
The Journal of Clinical Investigation