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J Clin Invest. 2012 Oct;122(10):3541-51. doi: 10.1172/JCI64151. Epub 2012 Sep 10.

MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity.

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1
Department of Cell Biology and Morphology, University of Lausanne, Lausanne, Switzerland.

Abstract

Pregnancy and obesity are frequently associated with diminished insulin sensitivity, which is normally compensated for by an expansion of the functional β cell mass that prevents chronic hyperglycemia and development of diabetes mellitus. The molecular basis underlying compensatory β cell mass expansion is largely unknown. We found in rodents that β cell mass expansion during pregnancy and obesity is associated with changes in the expression of several islet microRNAs, including miR-338-3p. In isolated pancreatic islets, we recapitulated the decreased miR-338-3p level observed in gestation and obesity by activating the G protein-coupled estrogen receptor GPR30 and the glucagon-like peptide 1 (GLP1) receptor. Blockade of miR-338-3p in β cells using specific anti-miR molecules mimicked gene expression changes occurring during β cell mass expansion and resulted in increased proliferation and improved survival both in vitro and in vivo. These findings point to a major role for miR-338-3p in compensatory β cell mass expansion occurring under different insulin resistance states.

PMID:
22996663
PMCID:
PMC3461923
DOI:
10.1172/JCI64151
[Indexed for MEDLINE]
Free PMC Article
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