cAMP-PKA dependent ERK1/2 activation is necessary for vanillic acid potentiated glucose-stimulated insulin secretion in pancreatic β-cells

Vanillic acid (VA), a dietary phenolic compound is generally studied for its anti-oxidative and anti-inflammatory effects. However, the effect of VA on insulin secretion and its mechanism of action has never been explored. In this study, we report that VA augments glucose-stimulated insulin secretion (GSIS) in both insulin-secreting cell-line INS-1 and isolated rat pancreatic islets. Potentiation of GSIS is accompanied by a concurrent increase in 3′,5′-cyclic adenosine monophosphate (cAMP) and activation of protein kinase A (PKA) in INS-1 and rat islets. The activated cAMP-PKA pathway, in turn, phosphorylates extracellular signal-regulated kinases 1/2 (ERK1/2) in INS-1 cells. Pharmacological intervention with PKA and ERK1/2 inhibitors revealed that VA potentiated GSIS is primarily dependent on PKA mediated ERK1/2 activity. These findings demonstrated that VA directly acts on insulin-secreting pancreatic β-cells to exert its insulinotropic effect thereby providing a novel role of VA in the regulation of insulin secretion.