Increased expression of miR-187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion.
Diabetologia
; 57(1): 122-8, 2014 Jan.
Article
en En
| MEDLINE
| ID: mdl-24149837
ABSTRACT
AIMS/HYPOTHESIS:
Type 2 diabetes is characterised by progressive beta cell dysfunction, with changes in gene expression playing a crucial role in its development. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and therefore alterations in miRNA levels may be involved in the deterioration of beta cell function.METHODS:
Global TaqMan arrays and individual TaqMan assays were used to measure islet miRNA expression in discovery (n = 20) and replication (n = 20) cohorts from individuals with and without type 2 diabetes. The role of specific dysregulated miRNAs in regulating insulin secretion, content and apoptosis was subsequently investigated in primary rat islets and INS-1 cells. Identification of miRNA targets was assessed using luciferase assays and by measuring mRNA levels.RESULTS:
In the discovery and replication cohorts miR-187 expression was found to be significantly increased in islets from individuals with type 2 diabetes compared with matched controls. An inverse correlation between miR-187 levels and glucose-stimulated insulin secretion (GSIS) was observed in islets from normoglycaemic donors. This correlation paralleled findings in primary rat islets and INS-1 cells where overexpression of miR-187 markedly decreased GSIS without affecting insulin content or apoptotic index. Finally, the gene encoding homeodomain-interacting protein kinase-3 (HIPK3), a known regulator of insulin secretion, was identified as a direct target of miR-187 and displayed reduced expression in islets from individuals with type 2 diabetes. CONCLUSIONS/INTERPRETATION:
Our findings suggest a role for miR-187 in the blunting of insulin secretion, potentially involving regulation of HIPK3, which occurs during the pathogenesis of type 2 diabetes.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
/
Glucosa
/
Insulina
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Animals
/
Humans
/
Middle aged
Idioma:
En
Revista:
Diabetologia
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido