1. MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity
- Author
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Jacovetti, Cecile, Abderrahmani, Amar, Parnaud, Geraldine, Jonas, Jean-Christophe, Peyot, Marie-Line, Cornu, Marion, Laybutt, Ross, Meugnier, Emmanuelle, Rome, Sophie, Thorens, Bernard, Prentki, Marc, Bosco, Domenico, and Regazzi, Romano
- Subjects
Obesity -- Genetic aspects -- Research -- Causes of -- Care and treatment ,Pregnancy -- Physiological aspects -- Genetic aspects -- Research ,Pancreatic beta cells -- Physiological aspects -- Research -- Genetic aspects ,MicroRNA -- Physiological aspects -- Research ,Health care industry - 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 ents 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 during13 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 compensatory0 cell mass expansion occurring under different insulin resistance states., Introduction Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia resulting from defective function and/or loss of insulin-secreting β cells (1), (2). These cells, located within the islets of [...]
- Published
- 2012
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