BACKGROUND:Morpholinosydnonimine, a nitric oxide (NO) donor, has been reported to inhibit insulin release in isolated pancreatic islets. We studied whether transdermal application of nitroglycerin, another NO donor widely used for angina prophylaxis, influenced glucose-stimulated insulin release in healthy, young, male volunteers. METHODS AND RESULTS:Oral glucose tolerance tests [(OGTT) 75 g glucose in 200 mL of water) were performed in the presence of placebo patches or nitroglycerin-releasing 'active' patches (approx. 0.4 mg hour-1 nitroglycerin) in the same patients with a 2-week intertest interval. Venous blood samples were taken before and 15, 30, 60, 90, 120 and 180 min after the glucose load and evaluated for plasma glucose level and immunoreactive insulin responses (radioimmunoassay). Glucose-stimulated maximum increase in plasma insulin immunoreactivity were 36.3 +/- 5 and 78.8 +/- 6.1 mU mL-1 (P < 0.05) in the presence of active and placebo patches, respectively. Nevertheless, both fasting and postload blood glucose levels were the same at either patch. Active patches significantly decreased blood pressure with a marginal increase in heart rate. CONCLUSION: We conclude that inhibition of glucose-stimulated insulin release by transdermal nitroglycerin without causing hyperglycaemia may serve as a novel component of the antianginal mechanism of action of nitrates.
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BACKGROUND:Morpholinosydnonimine, a nitric oxide (NO) donor, has been reported to inhibit insulin release in isolated pancreatic islets. We studied whether transdermal application of nitroglycerin, another NO donor widely used for angina prophylaxis, influenced glucose-stimulated insulin release in healthy, young, male volunteers. METHODS AND RESULTS: Oral glucose tolerance tests [(OGTT) 75 g glucose in 200 mL of water) were performed in the presence of placebo patches or nitroglycerin-releasing 'active' patches (approx. 0.4 mg hour-1 nitroglycerin) in the same patients with a 2-week intertest interval. Venous blood samples were taken before and 15, 30, 60, 90, 120 and 180 min after the glucose load and evaluated for plasma glucose level and immunoreactive insulin responses (radioimmunoassay). Glucose-stimulated maximum increase in plasma insulin immunoreactivity were 36.3 +/- 5 and 78.8 +/- 6.1 mU mL-1 (P < 0.05) in the presence of active and placebo patches, respectively. Nevertheless, both fasting and postload blood glucose levels were the same at either patch. Active patches significantly decreased blood pressure with a marginal increase in heart rate. CONCLUSION: We conclude that inhibition of glucose-stimulated insulin release by transdermal nitroglycerin without causing hyperglycaemia may serve as a novel component of the antianginal mechanism of action of nitrates.