Ghrelin inhibits insulin secretion through the AMPK-UCP2 pathway in beta cells.
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.
Wang
Ying
Y
The First Department of Medicine, Wakayama Medical University, Wakayama, Japan.
Nishi
Masahiro
M
Doi
Asako
A
Shono
Takeshi
T
Furukawa
Yasushi
Y
Shimada
Takeshi
T
Furuta
Hiroto
H
Sasaki
Hideyuki
H
Nanjo
Kishio
K
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000071246:Uncoupling Protein 2; D015854:Up-Regulation / Q000187:drug effects
D054439:Ghrelin; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D055372:AMP-Activated Protein Kinases; C516863:Ptprn protein, mouse; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005947:Glucose