Adaptive ß-Cell Neogenesis in the Adult Mouse in Response to Glucocorticoid-Induced Insulin Resistance

• Published in: Diabetes (New York, N.Y.) Vol. 68; no. 1; p. 95
• Main Authors: Courty, Emilie, Besseiche, Adrien, Huong Do, Thi Thu, Liboz, Alexandrine, Aguid, Fatima Mohamed, Gautier, Jean-François, Riveline, Jean-Pierre, Fève, Bruno, Guillemain, Ghislaine, Haumaitre, Cécile, Gourdy, Pierre, Quilichini, Evans, Buyse, Marion, Buscato, Melissa, Blondeau, Bertrand
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01-01-2019
• Subjects: Cells; Corticosterone; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Glucocorticoids; Insulin; Insulin resistance; Insulin secretion; Medical treatment; mRNA; Pancreas; Secretion; Sox9 protein
• ISSN: 0012-1797; 1939-327X

Both type 1 and type 2 diabetes are characterized by deficient insulin secretion and decreased ß-cell mass. Thus, regenerative strategies to increase ß-cell mass need to be developed. To characterize mechanisms of ß-cell plasticity, we studied a model of severe insulin resistance in the adult mouse and defined how ß-cells adapt. Chronic corticosterone (CORT) treatment was given to adult mice and led to rapid insulin resistance and adaptive increased insulin secretion. Adaptive and massive increase of ß-cell mass was observed during treatment up to 8 weeks. ß-Cell mass increase was partially reversible upon treatment cessation and reinduced upon subsequent treatment. ß-Cell neogenesis was suggested by an increased number of islets, mainly close to ducts, and increased Sox9 and Ngn3 mRNA levels in islets, but lineage-tracing experiments revealed that neoformed ß-cells did not derive from Sox9- or Ngn3-expressing cells. CORT treatment after ß-cell depletion partially restored ß-cells. Finally, ß-cell neogenesis was shown to be indirectly stimulated by CORT because serum from CORT-treated mice increased ß-cell differentiation in in vitro cultures of pancreatic buds. Altogether, the results present a novel model of ß-cell neogenesis in the adult mouse and identify the presence of neogenic factors in the serum of CORT-treated mice.