MicroRNA-7a regulates pancreatic ß cell function.
J Clin Invest
; 124(6): 2722-35, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24789908
ABSTRACT
Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic ß cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of ß cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in ß cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates ß cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in ß cells developed diabetes due to impaired insulin secretion and ß cell dedifferentiation. Interestingly, perturbation of miR-7a expression in ß cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine ß cell mass. Furthermore, we found that miR-7a levels are decreased in obese/diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated ß cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic ß cells and support a role for miR-7 in the adaptation of pancreatic ß cell function in obesity and type 2 diabetes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Células Secretoras de Insulina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article