The effect of a potassium (K+) channel opener (pinacidil) on serum insulin levels and blood glucose levels was investigated in normal volunteers during glucose loading. An intravenous glucose load was used with and without oral pretreatment: pinacidil (25 mg) 11 hours and 1 hour before the 25-g glucose loading. Serum insulin, C-peptide, blood glucose, and plasma catecholamines were measured between t = 0 and t = 180 minutes. Pinacidil led to significantly lower insulin levels, especially in the first phase. Serum C-peptide levels were not significantly lowered, and glucose levels were not changed. Pinacidil inhibits the first phase of insulin release after glucose administration in healthy volunteers. These findings suggest that the safety of the drug regarding glucose tolerance, should be tested separately in patients with diabetes mellitus and essential hypertension.