AICAR enhances insulin signaling via downregulation of miR-29.
Can J Physiol Pharmacol
; 94(2): 199-205, 2016 Feb.
Article
en En
| MEDLINE
| ID: mdl-26359920
ABSTRACT
As an activator of AMPK, the effect of AICAR on insulin signaling has not been investigated extensively. PI3K-Akt is a critical node involved in the insulin signaling pathway. We observed that concomitant with the activation of AMPK by AICAR, the protein level of PI3K p85α and the insulin-induced phosphorylation of Akt were enhanced in mouse primary hepatocytes. Previously, we identified a group of AMPK-regulated miRNAs in hepatocytes. It is not clear whether miRNAs are related to the regulation of insulin signaling by AMPK. Here, we confirmed the negative regulation of miR-29 family members by AICAR treatment in mouse primary hepatocytes. Our results indicated that p85α is a direct target of miR-29 and is negatively regulated by miR-29b in hepatocytes. In agreement with the findings in vitro, we found that the expression of miR-29 and the protein levels of p85α were inversely correlated in the liver of fasted mice. Overexpression of miR-29b reduced the insulin-induced phosphorylation of Akt in hepatocytes, suggesting that miR-29 could serve as a negative regulator of insulin signaling. Furthermore, we found that overexpression of miR-29 could attenuate the effect of AICAR on p85α expression. Taken together, our results indicated that activation of AMPK may enhance insulin signaling via downregulation of miR-29.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Can J Physiol Pharmacol
Año:
2016
Tipo del documento:
Article
País de afiliación:
China