SELECTIVE α2RECEPTOR BLOCKADE FACILITATES THE INSULIN RESPONSE TO ADRENALINE BUT NOT TO GLUCOSE IN MAN

The adrenergic nervous system plays an important role in the control of insulin release and animal work suggests that this is mediated by way of alpha 2 adrenoceptors. A specific alpha 2 adrenoceptor antagonist (idazoxan) is now available for use in man and we have studied its effects on insulin release in normal volunteers (a) during the infusion of adrenaline (0.05 micrograms/kg/min) and (b) after an intravenous dose of glucose (20 g). The infusion of adrenaline alone had no significant effect on insulin release while in the presence of idazoxan, insulin release was markedly stimulated by adrenaline. Despite this, adrenaline-induced hyperglycaemia was unaffected by pretreatment with idazoxan. In the second study, pretreatment with either idazoxan or a specific alpha 1 antagonist (prazosin) had no significant effect on either glucose tolerance, glucose-induced insulin release or glucose-induced suppression of glucagon. Intravenous glucose also had no significant effect on pancreatic polypeptide levels. Therefore the effect of adrenaline on insulin release is mediated by way of inhibitory alpha 2 adrenoceptors in the pancreas, while the release of insulin in response to glucose in a resting subject is independent of the alpha-adrenergic system.