Ghrelin inhibits insulin secretion through the AMPK–UCP2 pathway in β cells

• DOI: 10.1016/j.febslet.2010.02.069
• Publication Date: 2010-03-04T14:41:00Z
• Authors: Ying Wang; Masahiro Nishi; Asako Doi; Takeshi Shono; Yasushi Furukawa; Takeshi Shimada; Hiroto Furuta; Hideyuki Sasaki; Kishio Nanjo
• Keywords: 0303 health sciences; AMP-activated protein kinase; Insulin secretion; AMP-Activated Protein Kinases; Ghrelin; Ion Channels; Uncoupling protein 2; Cell Line; Up-Regulation; Enzyme Activation; Mitochondrial Proteins; Mice; 03 medical and health sciences; Glucose; Insulin-Secreting Cells; Insulin Secretion; Animals; Insulin; Receptor-Like Protein Tyrosine Phosphatases, Class 8; Uncoupling Protein 2; Signal Transduction

Ghrelin inhibits insulin secretion partly via induction of IA‐2β. 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‐2β pathway.