Inhibition of 2-deoxy-glucose-induced glucagon secretion by muscarinic and alpha-adrenoceptor blockade in the mouse.

Neuroglycopenia induced by 2-deoxy-glucose is known to activate the autonomic nervous system and to stimulate glucagon secretion. In this study, the relative contribution of the various branches of the autonomic nervous system on the 2-deoxy-glucose-induced glucagon secretion was investigated in the mouse. An intravenous injection of 2-deoxy-glucose (500 mg/kg) was followed by a 5-fold increase in plasma levels of glucagon (P less than 0.001). This 2-deoxy-glucose-induced glucagon secretion was impaired by pre-treatment with either the muscarinic antagonist methylatropine (by 83%; P less than 0.001) or the nicotinic antagonist hexamethonium (by 90%; P less than 0.001). Further, also the alpha-adrenoceptor antagonist phentolamine inhibited the glucagon response to 2-deoxy-glucose (by 35%; P less than 0.01). In contrast, the beta-adrenoceptor antagonist L-propranolol did not affect the glucagon response to 2-deoxy-glucose. It is concluded that the main mechanism behind the increased plasma levels of glucagon following administration of 2-deoxy-glucose is cholinergic activation. However, intact alpha-adrenoceptors are a pre-requisite for the full effect of 2-deoxy-glucose. In contrast, beta-adrenoceptors seem to be of no importance and there seems to be no room for neuropeptides as mediators of the neuroglycopenia-induced glucagon secretion in the mouse.