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MicroRNA-7a regulates pancreatic β cell function
Mathieu Latreille, … , Patrik Rorsman, Markus Stoffel
Mathieu Latreille, … , Patrik Rorsman, Markus Stoffel
Published May 1, 2014
Citation Information: J Clin Invest. 2014;124(6):2722-2735. https://doi.org/10.1172/JCI73066.
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Research Article Endocrinology Article has an altmetric score of 35

MicroRNA-7a regulates pancreatic β cell function

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Abstract

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.

Authors

Mathieu Latreille, Jean Hausser, Ina Stützer, Quan Zhang, Benoit Hastoy, Sofia Gargani, Julie Kerr-Conte, Francois Pattou, Mihaela Zavolan, Jonathan L.S. Esguerra, Lena Eliasson, Thomas Rülicke, Patrik Rorsman, Markus Stoffel

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Figure 3

miR-7 target identification in pancreatic β cells.

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miR-7 target identification in pancreatic β cells.
(A and B) Cumulative ...
(A and B) Cumulative density function (CDF) plots of log2-transformed gene expression fold change in (A) MIN6 cells infected with Ad–miR-7a2 vs. Ad-GFP control and (B) pancreatic islets of Rip-Cre Mir7a2fl/fl versus control mice. (A) P < 10–6 and (B) P < 10–3 for genes with matches to the miR-7 seed in their 3′-UTR (red line) and genes with matches to top ElMMo targets (green line) vs. genes lacking miR-7 seed matches (black line), 2-sided Mann-Whitney test. (C) Changes in gene expression of 9,385 genes expressed in Ad–miR-7a2–infected MIN6 cells vs. Rip-Cre Mir7a2fl/fl islets (r = –0.24; P < 1015, Pearson test). (D) GO term enrichment of genes down- and upregulated from Ad–miR-7a2–infected MIN6 cells and Rip-Cre Mir7a2fl/fl pancreatic islets (KO). Heatmap shows P values of all significantly enriched GO terms (columns) together with the gene sets (rows) in which the terms were enriched. The number of genes in each set is indicated in parentheses. (E) Scatter plot of log2-transformed gene expression fold change from Ad–miR-7a2–infected MIN6 cells vs. Rip-Cre Mir7a2fl/fl pancreatic islets within the GO classes Membrane and Secretion. Each gray dot represents a gene. Genes with miR-7 seed in their 3′-UTR are illustrated (red triangles).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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