Resveratrol, a naturally occurring phytoalexin, is known to exert numerous beneficial effects in the organism. Literature data indicate that this compound may, among other effects, play a role in prevention of diabetes and diabetic complications. Resveratrol was recently found to affect insulin secretion in vitro and to change blood insulin concentrations. These effects are, however, not fully elucidated. In the present study, 1, 10 and 100microM resveratrol incubated for 90min with pancreatic islets isolated from normal rats failed to affect basal insulin release, but substantially impaired the secretory response to physiological and maximally effective glucose. In depolarized islets exposed to resveratrol, succinate-induced insulin secretion was also diminished. The blockade of somatostatin receptors substantially enhanced insulin secretion induced by 6.7mM glucose and simultaneously suppressed the inhibitory effect of 1microM resveratrol, but at 10 and 100microM, resveratrol was still able to attenuate hormone secretion. Acetylcholine clearly increased the insulin-secretory response to 6.7mM glucose and canceled the inhibitory effect of 1microM resveratrol. However, resveratrol at concentrations 10 and 100microM strongly decreased insulin secretion. The direct activation of protein kinase C totally suppressed the inhibitory influence of 1 and 10microM resveratrol on hormone secretion. However, activation of this enzyme appeared to be insufficient to cancel the insulin-suppressive effect of 100microM resveratrol. These data indicate that resveratrol-induced inhibition of insulin secretion may be partially mitigated by suppression of somatostatin action, activation of protein kinase C or the presence of acetylcholine. The in vivo experiment revealed that resveratrol, administered to normal rats at the dose 50mg/kg body weight, diminished blood insulin concentrations at 30min, without concomitant changes in glycemia. These observations point to the direct insulin-suppressive action of resveratrol in the rat.