Hypoglycaemia insulin secretion inhibition

The naturally mediated inhibition of insulin secretion in response to hypoglycaemia is probably elicited after activation of cerebral glucosecep-tors (Rohner-Jeanrenaud et al., 1983) and through central noradrenergic pathways (McCaleb and Myers, 1982). The nerve fibres that enter the pancreas are mixed nerves (i.e. sympathetic and parasympathetic) derived from the splanchnic area and the N. vagus. These nerves generally accompany the superior pancreatic-duodenal vessels. Autonomic nerves have their terminals in close proximity to A- and B-cells (Ahren et al., 1986). 

Not fully established. An in vitro study using human liver microsomes indicated that erythromycin inhibits the metabolism (mono-A-dealkylation) of disopyramide which, in vivo, would be expected to reduce its loss from the body and increase its serum levels. Clarithromycin and azithromycin probably do the same. The increased serum levels of disopyramide can result in adverse effects such as QT prolongation and torsade de pointes, and may result in enhanced insulin secretion and hypoglycaemia. - Both intravenous erythromycin and clarithromycin" alone have been associated with prolongation of the QT interval and torsade de pointes. Therefore, disopyramide and macrolides may have additive effects on the QT interval in addition to the pharmacokinetic interaction. 

Disopyramide and its metabolite mono-isopropyl disopyramide T secretion of insulin (considered to be due to inhibition of potassium-ATP channels). Suggestion that disopyramide causes an impairment of the counterregulatory (homeostatic) mechanisms that follow hypoglycaemia... 

Hedeland H, Djmling J-F, Holrfelt B. Pharmacological inhibition of adrenaline secretion following insulin induced hypoglycaemia in man the effect of Catapresan. Acta Endocrinol (Copenh) (1971) 67, 97-103. 

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