1. MicroRNAs contribute to compensatory ß cell expansion during pregnancy and obesity
- Author
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Jacovetti Cécile, Abderrahmani Amar, Parnaud Géraldine, Jonas Jean Christophe, Peyot Marie Line, Cornu Marion, Laybutt Ross, Meugnier Emmanuelle, Rome Sophie, Thorens Bernard, Prentki Marc, Bosco Domenico, Regazzi Romano, Université de Lausanne (UNIL), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Surgery, University of Geneva [Switzerland], Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), St. Vincent's Hospital, Sydney, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), This work was supported by grants of the Swiss National Science Foundation (31003A-127254 to R. Regazzi, 32003B-120376 to D. Bosco), European Foundation for the Study of Diabetes (to R. Regazzi), Société Francophone du Diabète (to C. Jacovetti), National Health and Medical Research Council of Australia (1030715 to R. Laybutt), Fondation pour la Recherche Médicale (to S. Rome), Association Française de recherche sur les Myopathies (to S. Rome), Association Française de Diabétologie (to S. Rome), and Canadian Diabetes Association (to M. Prentki)., We thank Corinne Sinigaglia (Cell Isolation and Transplantation Center, Geneva University, Geneva, Switzerland) for technical assistance., Université de Lausanne = University of Lausanne (UNIL), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Université de Genève = University of Geneva (UNIGE), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Université de Montréal [Montréal], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
- Subjects
Male ,PLACENTAL-LACTOGEN ,[SDV]Life Sciences [q-bio] ,Estrogen receptor ,Receptors, G-Protein-Coupled ,Mice ,0302 clinical medicine ,Glucagon-Like Peptide 1 ,Pregnancy ,Receptors, Glucagon ,Receptor ,Fulvestrant ,Cells, Cultured ,0303 health sciences ,geography.geographical_feature_category ,Estradiol ,Postpartum Period ,Estrogen Antagonists ,PROLIFERATION ,Organ Size ,General Medicine ,Islet ,Adaptation, Physiological ,PROTEIN-COUPLED RECEPTOR ,ESTROGEN ,medicine.anatomical_structure ,PROBE LEVEL ,Cytokines ,Female ,GPER ,Signal Transduction ,Research Article ,EXPRESSION ,medicine.medical_specialty ,030209 endocrinology & metabolism ,Biology ,MASS ,INSULIN-SECRETION ,Glucagon-Like Peptide-1 Receptor ,Islets of Langerhans ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,microRNA ,medicine ,Animals ,Obesity ,Rats, Wistar ,030304 developmental biology ,geography ,Pancreatic islets ,DIABETES-MELLITUS ,PANCREATIC-ISLETS ,medicine.disease ,Mice, Mutant Strains ,Rats ,MicroRNAs ,Endocrinology ,Gene Expression Regulation ,Insulin Resistance - Abstract
International audience; 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.
- Published
- 2012
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