Effects of isoproterenol on insulin and glucagon secretion in rats treated chronically with isoproterenol

Abstract

To better understand the mechanism(s) whereby chronic adrenaline treatment rendered rats less susceptible to the hyperglycemic effect of this catecholamine sharing both α- and β-adrenergic activities, a similar treatment was done with isoproterenol, a pure β-adrenergic agonist (300 μg/kg daily for 28 days). The dynamics of plasma glucose, insulin, and glucagon were studied in unanesthetized control and treated rats during an isoproterenol infusion (0.75 μg kg−1 min−1), an acute intravenous glucose load (0.5 g/kg), or the simultaneous administration of both agents. Chronic treatment with isoproterenol did not modify the basal glucose and glucagon levels but it greatly diminished the insulin values (40.1 ± 3 vs. 59.6 ± 3.6 μU/mL, p < 0.01). In both groups, the isoproterenol infusion produced an increase in glucose concentration which was associated with a prompt rise in insulin levels; however, the glucose and insulin elevations were significantly lower in the isoproterenol-treated rats than in the control animals (p < 0.01). Despite these glucose and insulin increases, plasma glucagon concentrations similarly rose during the first 15 min of infusion in both groups, followed by a return to their basal levels. During the intravenous glucose tolerance test, the plasma glucose, insulin, and glucagon responses showed similar patterns in both groups of rats; however, during the concomitant isoproterenol infusion, the treated rats showed a better glucose tolerance than their controls. Similarities with results obtained with adrenaline treatment suggest that adaptation to the hyperglycemic effect of both catecholamines may be mediated by desensitization at the β-receptor level; furthermore, such a modification may lead to an increase in the sensitivity to insulin.