Effects of S-nitroso-N-acetyl-penicillamine administration on glucose tolerance and plasma levels of insulin and glucagon in the dog

It has been suggested that nitric oxide (NO, nitrogen monoxide) is a regula tor of carbohydrate metabolism in skeletal muscle. The present study was un dertaken to investigate the acute effects of the nitric oxide donor S-nitro so-N-acetylpenicillamine (SNAP) on blood glucose levels and on the gluco-re gulatory hormones insulin and glucagon in healthy dogs. The acute effects o f SNAP on mean arterial pressure and heart rate were also investigated. The drug was administered intravenously and the pre- and postprandial blood gl ucose, plasma insulin, and glucagon concentrations were determined at half- hour time intervals postadministration after a glucose challenge. The plasm a nitrate and nitrite concentrations were measured and taken as the biochem ical markers of in vivo NO formation. The oral glucose tolerance test revea led an impaired glucose tolerance in SNAP-treated dogs as reflected by the area under the glucose curve, 1150.50 +/- 63.00 mmol x 150 min and 1355.25 +/- 102.01 mmol/L x 150 min in dogs treated with 10 and 20 mg/kg of SNAP, r espectively, compared with 860.25 +/- 60.68 mmol/L x 150 min in captopril-t reated controls (P<0.05). The 2-h blood glucose concentration in dogs treat ed with 20 mg/kg body wt of SNAP was 9.17<plus/minus>1.10 mmol/L compared w ith 5.59 +/-0.26 mmol/L for captopril-treated controls (P=0.015). The oral glucose tolerance test also confirmed an impaired insulin secretion in the SNAP-treated dogs. While the plasma insulin concentration increased gradual ly in the captopril-treated controls to a peak value of 39.50 +/-2.55 rho I U/ml, 1.5 h after a glucose challenge there was a decrease in the plasma in sulin concentration in SNAP-treated dogs to a low value of 20.67 +/-0.88 mu IU/ml (P=0.006). In contrast, there were no significant differences in pla sma glucagon concentration in SNAP-treated dogs and captopril-treated dogs at any time points. Using the Griess reaction, we found that there was a 27 -95% increase in plasma nitrate/nitrite concentration on administration of SNAP. The sustained hyperglycemic effect observed in SNAP-treated dogs was accompanied by a marginal decrease in the mean arterial blood pressure and a significant increase in heart rate (P<0.05). We conclude that acute admin istration of SNAP in the oral glucose tolerance test releases NO that modul ates the parameters of carbohydrate metabolism. (C) 2001 Academic Press.