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 m eal were studied in the beagle dog. The alpha(2)-adrenoceptor antagoni st deriglidole (1 mg/kg po), administered 45 min before feeding, signi ficantly reduced glycemia and increased insulin, FFA, and glycerol lev els. Although the alpha(2)-adrenoceptor agonist UK-14.304 (3 mu g/kg s c), administered 15 min before feeding, had no effect per se, it compl etely blocked meal-induced insulin release, thus promoting a mild incr ease in glycemia, and prolonged the meal-induced FFA decrease. Derigli dole antagonized the reduction of insulin secretion and the hyperglyce mia induced by UK-14.304. The meal-induced fall in FFA levels was stil l observed after deriglidole treatment and was markedly amplified when UK-14.304 was administered with deriglidole. These results suggest th at, in the dog, insulin release and lipolysis are very sensitive to al pha(2)-adrenoceptor stimulation. It is also suggested that the meal-ev oked decrease in lipid mobilization results from an increase in alpha( 2)-adrenoceptor stimulation rather than from an increase in insulin se cretion.