The effect of nitric oxide released from s-nitroso-glutathoine on glucagon and insulin in dogs

ABSTRACT

Nitric oxide (NO), a potent modulator of cellular function, and NO donors have been useful tools in both experimental and clinical setting. Low molecular weight thiols such as cysteine and glutathoine were proposed to act as NO-carriers. The study was undertaken to investigate the pharmacological activity of the NO donor, S-nitrosoglutathoine (GSNO), on the plasma glucose and on the gluco-regulatory hormones, insulin and glucagon in healthy normoglycaemic dogs. Plasma glucose levels were measured by the glucose oxidase method, while the insulin and glucagon levels were determined by radioimmunoassay. In healthy normoglycaemic dogs, administration of 50 mg/kg GSNO caused an increase in post-prandial plasma glucose levels. The plasma glucose levels were significantly (p<0.05) elevated at 1.5 hr, 2.0 hr and 2.5 hr of the oral glucose tolerance test. These values were significantly higher than those obtained for the controls. The increase in glucose level was associated with a significant decrease in insulin levels and increase in glucagon levels (p<0.05). The fasting insulin level was 8.0 ñ 0.3 IU/ml in the control. The insulin level increased to a maximum of 34.0 ñ 0.3 IU/ml 1.5 hr post-prandial, and then decreased to 12.4 ñ 0.4 IU/ml after 2.5 hr. On administration of 50 mg/kg GSNO, the insulin level increased to a maximum of 23.0 ñ 0.6 IU/,l after 1.5 hr post-prandial and then decreased to 17.0 ñ 0.4 IU/ml after 2.5 hr. The blood glucagon levels increased from 40.0 ñ 0.3 pg/ml to 53.0 ñ 0.3 pg/ml after 1 hr in controls. In dogs administered with GSNO, the blood glucagon level increases to a maximum level of 80.0 ñ 0.5 pg/ml 1.5hr post-prandial. These results suggest that in healthy normoglycaemic dogs, nitric oxide released from GSNO caused a transient increase in post-prandial plasma glucose levels, inhibited glucose stimulated insulin secretion and elevated glucagon levels.(AU)