MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity.
(2012) Journal of Clinical Investigation — Vol. 122, n° 10, p. 3541-3551 (2012)
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- 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.
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Jacovetti, C., Abderrahmani, A., Parnaud, G., Jonas, J.-C., Peyot, M.-L., Cornu, M., Laybutt, R., Meugnier, E., Rome, S., Thorens, B., Prentki, M., Bosco, D., & Regazzi, R. (2012). MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity. Journal of Clinical Investigation, 122(10), 3541-3551. https://doi.org/10.1172/JCI64151 (Original work published 2012)