Inhibition of Insulin Release by Norepinephrine in Man

Abstract

Normal subjects were given glucose (300 mg/ min) or tolbutamide (1 g, intravenously), alone and during intravenous infusions of norepi-nephrine (6 lg/ min). Immunoreactive insulin concentration was less than expected during the infusions of norepinephrine, but returned to higher values after the norepinephrine infusions. From these data it is concluded that norepinephrine inhibits the release of insulin from pancreatic beta cells.

The physiological and pharmacological role of presynaptic alpha‐ and beta‐adrenoceptors in man.

“…If the similar affinities of idazoxan and guanfacine for the a2-adrenoceptor in rat cortical slices (Jarrott et al, 1982;Lane et al, 1983) are a measure of their affinity for peripheral presynaptic a-adrenoceptors in man, then the pharmacokinetic data in our study indeed suggest that the guanfacine concentration was adequate for guanfacine to compete successfully with idazoxan for these receptors by the end of its infusion. The persistent suppression of plasma insulin by guanfacine in the presence of idazoxan tends to support the idea that idazoxan was relatively ineffective against guanfacine in the periphery: the a2-adrenoceptor which mediates suppression of insulin release is peripheral, on the islet cells (Porte, 1966), and this is illustrated in Study 2 by the effect of adrenaline, which does not cross the blood-brain barrier. On the other hand, the effective blockade by idazoxan of the guanfacine induced increase in plasma growth hormone seems to confirm that idazoxan concentration in the CNS was adequate to antagonize the central actions of guanfacine.…”

Peroxisome proliferator-activated receptor γ coactivator-1-dependent uncoupling protein-2 expression in pancreatic islets of rats: a novel pathway for neural control of insulin secretion

“…Nutrients, hormones and neural signals are the main participants of this complex and integrated system [22]. Since early studies [23], noradrenergic stimulation of pancreatic islets is known to produce a net inhibitory effect upon insulin secretion. During the last three decades several studies have provided strong evidence that NE, acting through α2 adrenergic receptors expressed on the beta-cell surface, leads to reduced cAMP formation [24] and subsequently, to inhibition of the distal components of the insulin exocytotic machinery [9].…”

Autonomic regulation of islet hormone secretion - Implications for health and disease

“…Electrical activation of the sympathetic nerves further induces a large release of noradrenaline into the pancreatic veins [58]. Because exogenous treatment with noradrenaline inhibits glu-cose-stimulated insulin secretion [61], it has been assumed that it is noradrenaline which mediates the inhibitory action of electrical sympathetic activation on glucose-stimulated insulin secretion. This is supported by studies showing that a-adrenoceptor blockade by phentolamine counteracts the inhibition of glucose-stimulated insulin secretion by electrical nerve activation [57,59] and that a specific a 2 -adrenoceptor agonist, clonidine, inhibits glucose-stimulated insulin secretion [62].…”

“…Therefore, approaches using noradrenaline to mimic endogenously released noradrenaline or using a combined aadrenoceptor and b-adrenoceptor blockade are required to establish the contribution by noradrenaline to the effects of sympathetic nerve stimulation. It has thereby been established that under conditions of stimulated insulin secretion noradrenaline potently inhibits insulin secretion and therefore probably mediates this action of the sympathetic nerves [61,69]. In contrast, this does not, however, seem to be the case for basal insulin secretion because although sympathetic nerve stimulation clearly inhibits basal insulin secretion, a local infusion of noradrenaline into the pancreatic artery over a wide dose range increased, not reduced, insulin secretion in the dog [58].…”