Involvement of alpha(2)-adrenoceptors in metabolic and hormonal responses to a mixed meal in beagle dogs

The effects of alpha(2)-adrenoceptor blockade or activation on glucose, insulin, free fatty acids (FFA), and glycerol responses to a mixed meal were studied in the beagle dog. The alpha(2)-adrenoceptor antagonist deriglidole (1 mg/kg po), administered 45 min before feeding, significantly reduced glycemia and increased insulin, FFA, and glycerol levels. Although the alpha(2)-adrenoceptor agonist UK-14.304 (3 mu g/kg sc), administered 15 min before feeding, had no effect per se, it completely blocked meal-induced insulin release, thus promoting a mild increase in glycemia, and prolonged the meal-induced FFA decrease. Deriglidole antagonized the reduction of insulin secretion and the hyperglycemia induced by UK-14.304. The meal-induced fall in FFA levels was still observed after deriglidole treatment and was markedly amplified when UK-14.304 was administered with deriglidole. These results suggest that, in the dog, insulin release and lipolysis are very sensitive to alpha(2)-adrenoceptor stimulation. It is also suggested that the meal-evoked decrease in lipid mobilization results from an increase in alpha(2)-adrenoceptor stimulation rather than from an increase in insulin secretion.