title: MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity.
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.
authors.affiliation: Department of Cell Biology and Morphology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Cécile
authors.initials: C
authors.lastname: Jacovetti
authors.forename: Amar
authors.initials: A
authors.lastname: Abderrahmani
authors.forename: Géraldine
authors.initials: G
authors.lastname: Parnaud
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Jonas
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Peyot
authors.forename: Marion
authors.initials: M
authors.lastname: Cornu
authors.forename: Ross
authors.initials: R
authors.lastname: Laybutt
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Meugnier
authors.forename: Sophie
authors.initials: S
authors.lastname: Rome
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
authors.forename: Marc
authors.initials: M
authors.lastname: Prentki
authors.forename: Domenico
authors.initials: D
authors.lastname: Bosco
authors.forename: Romano
authors.initials: R
authors.lastname: Regazzi
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D000067757:Glucagon-Like Peptide-1 Receptor; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000473:pathology* / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D018027:Receptors, Glucagon / Q000819:agonists / Q000172:deficiency; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D016207:Cytokines; D004965:Estrogen Antagonists; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; C520305:Gper1 protein, rat; C555034:MIRN144 microRNA, rat; C573089:MIRN338 microRNA, rat; C555035:MIRN451A microRNA, rat; D035683:MicroRNAs; D043562:Receptors, G-Protein-Coupled; D018027:Receptors, Glucagon; D000077267:Fulvestrant; D004958:Estradiol; D052216:Glucagon-Like Peptide 1