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

Abstract

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 micrograms/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.

Effects of acute α2-blockade on insulin action and secretion in humans

“…The observation that none of these parameters showed any significant differences between placebo and deriglidole for 60 min after drug administration led us to the conclusion that, in healthy individuals, neither basal insulin secretion nor lipolysis are affected by acute ␣ 2 -blockade. Thus, in the postabsorptive state, ␤-cells do not appear to be under tonic adrenergic inhibition, in agreement with previous work in rats (13) and in contrast to recent experimental work in dogs (12) and the finding of Robertson and Porte (28). The latter study was done in six subjects with a wide weight range (from 91 to 133%) of ideal body weight, and phentolamine infusion was associated with a very small rise in plasma insulin (from 10 to 12 µU/ml).…”

“…INSULIN ACTION AND SECRETION DURING ␣ 2 -BLOCKADE of deriglidole results in a prompt (within 30 min) increase in plasma insulin and FFA concentrations (12). The higher dose used (1 mg/kg) or species differences might explain these discrepancies.…”