Journal Article

MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity

Cornu, Marion, Prentki, Marc, Jonas, Jean-Christophe, Laybutt, Ross, Abderrahmani, Amar, Meugnier, Emmanuelle, Peyot, Marie-Line, Regazzi, Romano, Parnaud, Géraldine, Bosco, Domenico, Jacovetti, Cécile, Rome, Sophie, Thorens, Bernard

2012

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Adaptation, Physiological - physiology / Animals / Care and treatment / Causes of / Cells, Cultured - drug effects / Cells, Cultured - metabolism / Cytokines - biosynthesis / Cytokines - genetics / Estradiol - analogs & derivatives / Estradiol - pharmacology / Estradiol - physiology / Estrogen Antagonists - pharmacology / Female / Fulvestrant / Gene Expression Regulation - physiology / Genetic aspects / Glucagon-Like Peptide 1 - physiology / Glucagon-Like Peptide-1 Receptor / Insulin Resistance - physiology / Islets of Langerhans - growth & development / Islets of Langerhans - metabolism / Islets of Langerhans - pathology / Life Sciences / Male / Mice / Mice, Mutant Strains / MicroRNA / MicroRNAs - biosynthesis / MicroRNAs - genetics / MicroRNAs - physiology / Obesity / Obesity - pathology / Obesity - physiopathology / Organ Size - drug effects / Pancreatic beta cells / Physiological aspects / Postpartum Period - metabolism / Pregnancy / Pregnancy - metabolism / Pregnancy - physiology / Rats / Rats, Wistar / Receptors, G-Protein-Coupled - agonists / Receptors, G-Protein-Coupled - biosynthesis / Receptors, G-Protein-Coupled - genetics / Receptors, Glucagon - agonists / Receptors, Glucagon - deficiency / Signal Transduction - drug effects / Signal Transduction - physiology