RT Journal Article
SR Electronic
T1 Adaptive β-Cell Neogenesis in the Adult Mouse in Response to Glucocorticoid-Induced Insulin Resistance
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 95
OP 108
DO 10.2337/db17-1314
VO 68
IS 1
A1 Courty, Emilie
A1 Besseiche, Adrien
A1 Do, Thi Thu Huong
A1 Liboz, Alexandrine
A1 Aguid, Fatima Mohamed
A1 Quilichini, Evans
A1 Buscato, Melissa
A1 Gourdy, Pierre
A1 Gautier, Jean-François
A1 Riveline, Jean-Pierre
A1 Haumaitre, Cécile
A1 Buyse, Marion
A1 Fève, Bruno
A1 Guillemain, Ghislaine
A1 Blondeau, Bertrand
YR 2019
UL http://diabetes.diabetesjournals.org/content/68/1/95.abstract
AB Both type 1 and type 2 diabetes are characterized by deficient insulin secretion and decreased β-cell mass. Thus, regenerative strategies to increase β-cell mass need to be developed. To characterize mechanisms of β-cell plasticity, we studied a model of severe insulin resistance in the adult mouse and defined how β-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 β-cell mass was observed during treatment up to 8 weeks. β-Cell mass increase was partially reversible upon treatment cessation and reinduced upon subsequent treatment. β-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 β-cells did not derive from Sox9- or Ngn3-expressing cells. CORT treatment after β-cell depletion partially restored β-cells. Finally, β-cell neogenesis was shown to be indirectly stimulated by CORT because serum from CORT-treated mice increased β-cell differentiation in in vitro cultures of pancreatic buds. Altogether, the results present a novel model of β-cell neogenesis in the adult mouse and identify the presence of neogenic factors in the serum of CORT-treated mice.