THE EFFECT OF FASTING ON THE HYPERGLYCAEMIC RESPONSES TO CATECHOL AMINES IN RATS.

The relative activities of adrenaline, noradrenaline and isoprenaline in producing hyperglycaemia and glycogenolysis in skeletal muscle have been studied in both fed and fasted rats, 1 hr after subcutaneous injection of the catechol amines. The relative hyperglycaemic activities of the three catechol amines depended greatly upon the prandial state of the rats and on the dose range used. In fed rats the relative potencies were in the descending order of potency, adrenaline-noradrenaline-isoprenaline, irrespective of the dose range. Isoprenaline had no hyperglycaemic activity in fed rats even at doses as high as 2 mg/kg. In fasted rats the order of potency depended on the dose. At low doses (0.005 to 0.02 mg/kg) the descending order was isoprenaline-adrenaline-noradrenaline. At higher doses (0.1 to 1 mg/kg) the descending order was adrenaline-isoprenaline-noradrenaline. The relative activities of the three catechol amines in causing glycogenolysis in muscle was independent of the dose range or the prandial state of the rats. Under all conditions the descending order of potency was isoprenaline-adrenaline-noradrenaline. The results are discussed with reference to Ahlquist's (1948) hypothesis of alpha- and beta- receptors and were consistent with the concept that, in the rat, liver glycogenolysis is mediated predominantly by alpha-receptors and muscle glycogenolysis mainly by beta-receptors. In general the hyperglycaemic response in the fed rat is mediated predominantly by alpha-receptors and in the fasted rat the response is mainly due to the activation of beta-receptors. A drug possessing both alpha- and beta-receptor activity elicits an exception to this rule in the fasted rat. Several perturbing problems in the literature, particularly with regard to the hyperglycaemic activity of isoprenaline and to the difficulty in blocking the hyperglycaemic response, can now be explained in the light of these findings.