Effects of autonomic blockade by methylatropine and optical isomers of propranolol on plasma insulin levels in the basal state and after stimulation

Abstract

The effects of autonomic blockade on plasma concentrations of immunoreactive insulin in the basal state and after stimulation with 4 different secretagogues were investigated in vivo in conscious mice. The muscarinic blocker methylatropine slightly depressed basal insulin, and almost totally abolished the insulin response to the cholinergic agonist carbachol, whereas the insulin response to glucose and glucagon was unaffected. Contrary to these findings, the insulin response to the β₂-adrenoceptor agonist terbutaline was potentiated, by about 75%. The β-adreneceptor blocker l-propranolol depressed basal insulin by about 60%, and totally abolished the insulin responses to glucagon and terbutaline. The insulin response to glucose was slightly reduced and that to carbachol was unaffected by l-propranolol. The stereoisomer d-propranolol which is devoid of β-adrenoceptor blocking activity but exerts local anaesthetic effect of the same potency as the lpisomer, was without effect on basal insulin levels and the insulin responses to the different secretagogues. It is concluded that basal concentrations of immunoreactive insulin is substantially dependent on intact β-adrenoceptros and more moderately dependent on intact muscarinic receptors. The insulin responses to terbutaline and glucagon are closely connected to the β-adrenoceptors, and the response to carbachol to the muscarinic receptors. Glucose-induced insulin response seems largely unaffected by autonomic receptor blockade although a slight reduction after β-adrenoceptor blockade is demonstrable.