Adaptive ß-Cell Neogenesis in the Adult Mouse in Response to Glucocorticoid-Induced Insulin Resistance.
Diabetes
; 68(1): 95-108, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30327384
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Secretoras de Insulina
/
Glucocorticoides
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2019
Tipo de documento:
Article