5′-AMP-activated protein kinase plays an essential role in geniposide-regulated glucose-stimulated insulin secretion in rat pancreatic INS-1 β cells
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Our previous work showed that geniposide affected glucose-stimulated insulin secretion (GSIS) via regulating glucose uptake and metabolism in pancreatic β cells; however, the molecular mechanisms remain largely unknown. Substantial evidence suggests that activation of 5′-AMP-activated protein kinase (AMPK) plays a central role in GSIS. Here, we aim to determine the role of AMPK on geniposide-regulated GSIS in rat pancreatic INS-1 cells. The results demonstrated that 6-[4-(2-piperidin-1-yletoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-α] pyrimidine (Compound C; an AMPK inhibitor) significantly attenuated the effects of geniposide on glucose uptake, energy metabolism, and insulin secretion in INS-1 cells. We also observed that geniposide induced phosphorylation of acetyl-CoA carboxylase (ACC), a marker of AMPK activity, in a time-dependent manner in INS-1 cells; however, in the presence of Compound C, the influence of geniposide on ACC phosphorylation was obviously inhibited. Furthermore, the knockdown of AMPK protein with AMPK siRNA treatment decreased the effects of geniposide on glucose uptake, adenosine triphosphate production, and GSIS. All these data indicate that AMPK plays an essential role in geniposide-regulated GSIS in pancreatic β cells.
KeywordsAcetyl-CoA carboxylase (ACC) 5′-AMP-activated protein kinase (AMPK) Geniposide Glucose-stimulated insulin secretion (GSIS)
This work was supported by grants from National Natural Science Foundation of China (81373459), Chongqing Science and Technology Committee (CSTC, 2015jcyjbx0064), Chongqing Science Found for Distinguished Young Scholars (2014jcyjjq10003), the Innovation of Science and Technology Leading Talent in Chongqing (2014kjcxljrc0018), and the Innovative Research Team Development Program at the University of Chongqing (CXTDX201601031).
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Conflict of interest
The authors disclose that there is no conflict of interest.
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