Ghrelin inhibits insulin secretion partly via induction of IA-2beta. However, the orexigenic effect of ghrelin is mediated by the AMP-activated protein kinase (AMPK)-uncoupling protein 2 (UCP2) pathway. Here, we demonstrate that ghrelin's inhibitory effect on insulin secretion also occurs through the AMPK-UCP2 pathway. Ghrelin increased AMPK phosphorylation and UCP2 mRNA expression in MIN6 insulinoma cells. Overexpression or downregulation of UCP2 attenuated or enhanced insulin secretion, respectively. Furthermore, AMPK activator had a similar effect to ghrelin on UCP2 and insulin secretion in MIN6 cells. In conclusion, ghrelin's inhibitory effect on insulin secretion is partly mediated by the AMPK-UCP2 pathway, which is independent of the IA-2beta pathway.
AMP-Activated Protein Kinases Animals