CONCENTRATION-DEPENDENT EFFECTS OF ADRENALINE ON THE PROFILE OF INSULIN-SECRETION FROM ISOLATED HUMAN ISLETS OF LANGERHANS

The effects of the mixed alpha/beta-agonist adrenaline on insulin secr etion from isolated human islets of Langerhans were studied. In static incubation experiments, adrenaline (0.1 nmol/l to 10 mu mol/l) caused a concentration-dependent inhibition of glucose-induced insulin secre tion from isolated human islets. However, perifusion experiments revea led that the time-course of the secretory changes induced by adrenalin e was complex. When employed at a high concentration (1 mu mol/l), adr enaline caused a sustained inhibition of glucose-induced insulin secre tion, which could be relieved by the addition of the alpha(2)-antagoni st yohimbine (10 mu mol/l). By contrast, infusion of adrenaline at a l ower concentration (10 nmol/l ), produced a large initial potentiation of glucose-induced insulin secretion. This response was, however, sho rt-lived and followed by sustained inhibition of secretion, which coul d be relieved by yohimbine (10 mu mol/l). The initial stimulation of i nsulin secretion provoked by 10 mu mol/l adrenaline/l was abolished wh en islets were incubated in the presence of the beta-antagonist, propr anolol (1 mu mol/l), consistent with activation of beta-adrenoceptors. In support of this, treatment of human islets with the selective beta (2)-agonist clenbuterol, was also associated with marked stimulation o f insulin secretion. By contrast, each of two selective beta(3)-agonis ts tested failed to alter insulin secretion from human islets. The res ults indicate that human pancreatic B-cells are equipped with both alp ha(2) and beta(2)-adrenoceptors which can affect insulin secretion. Ad renaline interacts with both of these but the alpha(2)-response is pre dominant and can overcome the tendency of beta(2)-adrenoceptors to pot entiate insulin release.