Alpha-adrenergic system in the modulation of pancreatic A and B cell function in normal rats

The role of the alpha-adrenergic system in the control of pancreatic A and B cell function was investigated in an isolated perfused rat pancreas model. Two experimental procedures were performed. In the first one we evaluated the effects of two distinct concentrations (10(-8) M and 10(-7) M) of five adrenergic substances, with varying degrees of potency on the alpha-adrenergic presynaptic receptor, on insulin (IRI) and glucagon (IRG) release induced by arginine (20 mM) plus glucose (6.6 mM). In the second procedure we studied the effects of the two alpha-blocking agents yohimbine (alpha 2-blocker) and prazosin (alpha 1-blocker) at 10(-7) M on epinephrine-modulated IRI and IRG response to the same combined metabolic stimulus. The inhibitory activity on basal and metabolically induced IRI secretion of the agonists was superimposable on their potency on the presynaptic alpha 2-adrenergic receptors. Similarly, the alpha 1-blocking agent prazosin was less effective than the alpha 2-blocker yohimbine in counteracting the inhibitory effects of epinephrine on basal and arginine plus glucose-induced insulin release. The alpha-cell activity was clearly stimulated by epinephrine, whereas selective alpha-adrenergic drugs showed no significant action on IRG secretion. Both alpha-blockers were ineffective on basal IRG release, while they had some potentiating effect on the epinephrine-induced glucagon release in basal state and during the metabolic stimulus, without a significant difference between the two drugs. We conclude that, at least in the isolated perfused rat pancreas, alpha 2-adrenergic receptors are involved in the inhibition of IRI release induced by catecholamines. On the contrary, the alpha-adrenergic system does not seem to play an essential role in the regulation of IRG secretion; the potentiation of the epinephrine-induced stimulation of A cell function by the alpha-adrenergic blockade could be accounted for by a greater availability of the catecholamine at the beta-receptor binding sites.