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Possible Role of AMPK/SIRT1 Signaling on Energy Balance in Geniposide- Treated INS-1 Cells

Abstract

Lixia Guo, Chunyan Liu, Fei Yin and Jianhui Liu

Our previous work showed that in pancreatic INS-1 cells, geniposide exerted a contrary role on both glucosestimulated insulin secretion (GSIS) and glucose uptake and metabolism in the presence of low and high glucose. But the molecular mechanisms are presently not well understood. In the present study, we design to probe the role of AMP-activated protein kinase (AMPK) and NAD+- dependent deacetylase sirtuin-1 (SIRT1) on geniposide regulating GSIS, and analyze the interaction between AMPK and SIRT1 in pancreatic β cells. Our results indicate that geniposide induce the phosphorylation of AMPK and enhance the expression of SIRT1 in the presence of low concentration of glucose, but in the presence of high concentrations of glucose, geniposide played a contrary role on those. Furthermore, Compound C (an AMPK inhibitor) and Ex527 (a potent and selective inhibitor of SIRT1) prevent the effects of geniposide on glucose uptake, ATP production and GSIS in INS-1 cells. Taken together, our findings suggest that AMPK/SIRT1 are associated with the role of geniposide on energy balance in INS-1 cells.