Resveratrol enhances insulin secretion by blocking KATP and KV channels of beta cells

The present study investigated the effect of resveratrol on the electrophysiology and insulin secretion of pancreatic beta cells, and examined resveratrol-induced alterations in insulin levels and plasma glucose of normal and streptozotocin-induced diabetic rats. Whole-cell voltage clamp study in the MIN6 cell, a mouse β cell line, revealed that resveratrol significantly inhibited ATP-sensitive K+ current at 3 μmol/l, and voltage-gated K+ currents at 30 μmol/l. Ca2+-activated K+ current was activated by resveratrol at 100 μmol/l. In MIN6 cells stained with membrane potential dye DiBAC4(5), resveratrol markedly depolarized membrane potential at the concentrations of 3–100 μmol/l. Insulin secretion was increased in the presence of resveratrol in MIN6, Hit-T15, and RIN-m5F cells. Resveratrol (3 mg/kg, i.p.) increased insulin secretion associated with a lowering in plasma glucose in normal rats, but not in streptozotocin-diabetic rats within the initial 60 min. In conclusion, resveratrol can act as an insulin-secretagogue through IKATP and IKV inhibition which can contribute to plasma glucose lowering effect in normal rats.