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

Abstract 

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.

Abbreviations: AICAR, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside, AMPK, AMP-activated protein kinase, GHSR, growth-hormone secretagogue receptor, GSIS, glucose-stimulated insulin secretion, KRBH, Krebs–Ringer bicarbonate–Hepes buffer, PPAR, peroxisome proliferator-activated receptor, PGC-1α, PPAR-γ coactivator-1-alpha, QT-PCR, quantitative real-time PCR, ROS, reactive oxygen species, siRNA, short-interfering RNA, UCP2, uncoupling protein 2

Keywords: Ghrelin, AMP-activated protein kinase, Uncoupling protein 2, Insulin secretion