Concentration-dependent effects of adrenaline on the profile of insulin secretion from isolated human islets of Langerhans

Abstract

The effects of the mixed alpha/beta-agonist adrenaline on insulin secretion from isolated human islets of Langerhans were studied. In static incubation experiments, adrenaline (0.1 nmol/l to 10 mumol/l) caused a concentration-dependent inhibition of glucose-induced insulin secretion from isolated human islets. However, perifusion experiments revealed that the time-course of the secretory changes induced by adrenaline was complex. When employed at a high concentration (1 mumol/l), adrenaline caused a sustained inhibition of glucose-induced insulin secretion, which could be relieved by the addition of the alpha 2-antagonist yohimbine (10 mumol/l). By contrast, infusion of adrenaline at a lower concentration (10 nmol/l), produced a large initial potentiation of glucose-induced insulin secretion. This response was, however, short-lived and followed by sustained inhibition of secretion, which could be relieved by yohimbine (10 mumol/l). The initial stimulation of insulin secretion provoked by 10 nmol adrenaline/l was abolished when islets were incubated in the presence of the beta-antagonist, propranolol (1 mumol/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 of insulin secretion. By contrast, each of two selective beta 3-agonists tested failed to alter insulin secretion from human islets. The results indicate that human pancreatic B-cells are equipped with both alpha 2- and beta 2-adrenoceptors which can affect insulin secretion. Adrenaline interacts with both of these but the alpha 2-response is predominant and can overcome the tendency of beta 2-adrenoceptors to potentiate insulin release.

AP2-NR4A3 transgenic mice display reduced serum epinephrine because of increased catecholamine catabolism in adipose tissue

“…Decreased adrenergic tone could account for elevated fasting glucose and poor glucose tolerance in transgenic mice. Although ␣-adrenergic receptor agonism has been shown to decrease glucose-stimulated insulin secretion, ␤-adrenergic receptor agonism potentiates pancreatic insulin secretion under certain conditions (1,7,17,18,26,29). Furthermore, decreased serum epinephrine may also account for decreased muscle insulin sensitivity in AP2-NR4A3 mice since proper adrenergic tone may be required for optimal insulin signaling in skeletal muscle.…”

Decreased α2-adrenergic receptor in the brain stem and pancreatic islets during pancreatic regeneration in weanling rats

“…Adrenal medullary hormones inhibit insulin release via the mediation of a2-adrenergic receptor (Lacey et al, 1993). The pancreatic islet [3-cells have more a2-than at-adrenergic receptors (Ahren, 2000).…”

“…a2-Adrenoceptor stimulation by the endogenous catecholamines could lead to inhibition of insulin release, masking any potentiated response that otherwise should have appeared from a t -and [3-adrenoceptor stimulation (Garcia-Barrado et al, 1998). In diabetic condition, a2A receptors are more activated which brought out the insulin inhibition and in turn hyperglycaemia (Lacey et al, 1993). Although there are reports, which say the role of brain a2-adrenergic receptors in the insulin secretion, there are not much studies about the inhibitory action of this receptor subtype on the islet DNA synthesis.…”

Differential effects of genistein on apoptosis induced by fluoride and pertussis toxin in human and rat pancreatic islets and RINm5F cells

“…Islets from heart-beating cadaver organ donors were isolated in the islet-transplant laboratory, University of Leicester (Leicester, UK) and transported to our laboratory in tissue culture medium (Lacey et al 1990, 1993, Loweth et al 1998. They were then cultured for a further 2-3 days in RPMI-1640 medium containing glucose (11·1 mM), -glutamine (300 µg/ml), sodium penicillin G (100 U/ml), streptomycin sulphate (100 µg/ml) and 10% (v/v) foetal bovine serum.…”