Role of α1‐ and α2‐adrenoceptors in catecholamine‐induced hyperglycaemia, lipolysis and insulin secretion in conscious fasted rabbits

Abstract

In conscious fasted rabbits an intravenous infusion of clonidine (2 μg kg−1 min−1) induced hyperglycaemia. The increase in blood glucose was accompanied by an inhibition of insulin secretion and basal lipolysis. Yohimbine infused at a rate of 20 μg kg−1 min−1 suppressed clonidine‐induced hyperglycaemia and blocked the inhibitory effect on insulin secretion mediated by the α2‐adrenoceptor agonist. The intravenous infusion of amidephrine (10 μg kg−1 min−1) induced an increase in insulin secretion in the absence of patent hyperglycaemia. Prazosin, 0.3 mg kg−1 s.c. selectively antagonized the effect of amidephrine on insulin secretion. Isoprenaline infusion (4.4 μg kg−1 min−1) evoked a significant increase in blood glycerol and immunoreactive insulin plasma levels. Both responses were clearly attenuated when α2‐adrenoceptors were simultaneously stimulated by selective (clonidine) and less selective (phenylephrine, 20 μg kg−1 min−1) agonists. Amidephrine infusion did not induce appreciable changes in blood glycerol nor did it modify, isoprenaline‐induced lipolytic response. Simultaneous infusion of isoprenaline and amidephrine induced a remarkable increase in insulin secretion. It is concluded that in normal fasted rabbits stimulation of α2‐adrenoceptors depresses basal and β‐adrenoceptor mediated lipolysis and insulin secretion. On the other hand, selective stimulation of α1‐adrenoceptors does not affect lipolysis but induces insulin release. Simultaneous stimulation of α1‐ and β‐adrenoceptors potentiates the insulin secretory response. 1988 British Pharmacological Society