Effects of chronic sodium salicylate feeding on the impaired glucagon and epinephrine responses to insulin-induced hypoglycaemia in streptozotocin diabetic rats.

Abstract

The potential role of endogenous prostaglandins in glucagon and epinephrine responses to insulin-induced hypoglycaemia was studied in streptozotocin-diabetic and age-matched control adult male rats. Rats made diabetic with a single intravenous injection of streptozotocin (65 mg/kg) developed impaired glucagon and epinephrine responses to insulin-induced hypoglycaemia by 80-100 days. Plasma glucagon levels in response to insulin-induced hypoglycaemia in streptozotocin-diabetic rats (167 +/- 67 pg/ml) were significantly lower (p less than 0.01) than those in control rats (929 +/- 272 pg/ml). Similarly, plasma epinephrine levels in hypoglycaemic state in streptozotocin-diabetic rats (11 +/- 8 pmol/ml) were also significantly lower (p less than 0.01) compared to control rats (37 +/- 13 pmol/ml). Streptozotocin-diabetic rats provided with sodium salicylate (25 mg/100 ml) in their drinking water from day one of diabetes exhibited prevention of the blunted glucagon and epinephrine responses to insulin-induced hypoglycaemia. About 80-100 days after the chronic sodium salicylate treatment in streptozotocin-diabetic rats, both plasma glucagon levels (1080 +/- 169 pg/ml) and plasma epinephrine levels (39 +/- 8 pmol/ml) were essentially identical to plasma glucagon levels (1074 +/- 134 pg/ml) and plasma epinephrine levels (37 +/- 5 pmol/ml) in control rats in hypoglycaemic state. These animals also exhibited an improvement in the diabetic state in that they had less severe hyperglycaemia and lack of weight gain. These results suggest that the blunted glucagon and epinephrine responses to insulin-induced hypoglycaemia may be related to altered prostaglandin levels in streptozotocin-diabetes.