SELECTIVE STIMULATION OF GLUCAGON-SECRETION BY BETA-2-ADRENOCEPTORS IN ISOLATED ISLETS OF LANGERHANS OF THE RAT

1 In rat isolated islets of Langerhans the selective beta-2-adrenoceptor agonist, clenbuterol (1 to 20-mu-M), significantly increased the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) within 2 min of incubation. 2 The cyclic AMP response to clenbuterol was inhibited in the presence of the selective beta-2 adrenoceptor antagonist, ICI 118551 (0.1 or 10-mu-M) but remained unchanged when the beta-1-antagonist, atenolol (0.1-mu-M) was administered. 3 Despite causing an elevation in cyclic AMP, clenbuterol (up to 20-mu-M) failed to influence insulin secretion at any glucose concentration tested, even in the presence of a phosphodiesterase inhibitor. 4 By contrast, clenbuterol elicited a dose-dependent rise in the rate of glucagon secretion; the maximal agonist-induced increase in secretion was two fold, a response equivalent to that observed with 20 mM L-arginine. 5 ICI 118551 significantly inhibited the rise in glucagon secretion induced by clenbuterol (up to 20-mu-M). 6 The results indicate that the rat islet A cell population is equipped with functional beta-2-adrenoceptors which influence glucagon secretion via the second messenger cyclic AMP, but that the B cells are deficient in functional beta-receptors.