Effect of ICI 66082, A β-adrenoceptor blocking drug on blood glucose in the rat

Abstract

ICI 66082, a cardioselective β-adrenoceptor blocking agent, was found to produce hypoglycaemia in fasted rats. In fed rats a hyperglycaemic response was observed. The drug produced hypoglycaemia in fed adrenalectomised animals. The hypoglycaemic response to ICI 66082 was accompanied by elevations in plasma immunoreactive insulin (IRI) concentrations. The drug also reduced plasma glucose and increased IRI in moderately alloxan-diabetic rats. In severely diabetic animals the drug did not increase IRI concentrations and did not unequivocally lower plasma glucose concentrations. In vitro experiments showed ICI 66082 to increase glucose uptake by rat diaphragm muscle and epididymal adipose tissue. The hypoglycaemic response may be mediated by increases in plasma IRI concentrations with a possible contribution from direct effects of the drug on peripheral glucose utilization. As these responses differ from those published in relatio nto other β-adrenoceptor blocking drugs it is unlikely that the effects are due to β-adrenoceptor blockade. However, like other β-adrenoceptor blocking drugs ICI 66082 reduced isoprenaline-mediated increase in plasma IRI.