Blocking effect of naloxone, dihydroergotamine and adrenalectomy in lithium-induced hyperglycaemia and glucose intolerance in the rat

Abstract

The direct effect of lithium administration on plasma glucose levels and glucose-induced insulin release, and the role of opioid and amine systems in these effects were examined in rats. Naloxone, an opiate antagonist, and dihydroergotamine, an alpha-adrenergic blocking agent, reversed the hyperglycaemia as well as the inhibition of glucose-stimulated insulin release induced by lithium. In adrenalectomized rats, administration of lithium induced hypoglycaemia and not hyperglycaemia as in the intact rats. The results suggest that the interaction of secreted endorphins with the sympathetic nervous system is the likely cause of the hyperglycaemia and the inhibition of the glucose-stimulated insulin release induced by lithium.

Role of adrenoceptors in vitro and in vivo in the effects of lithium on blood glucose levels and insulin secretion in the rat

“…The effect of lithium relevant to the present study is the induction of marked hyperglycaemia with inappropriately low plasma IRI levels and impaired glucose tolerance (Bhattacharya, 1964;Plenge et al, 1970;Mellerup et al, 1970;Fontela et al, 1986). In addition, lithium impairs IRI secretion in vitro, glucose-induced IRI being partially inhibited by lithium (Anderson & Blackard, 1978;Fontela et al, 1987).…”

“…In addition, lithium impairs IRI secretion in vitro, glucose-induced IRI being partially inhibited by lithium (Anderson & Blackard, 1978;Fontela et al, 1987). The participation of the adrenal medulla in the effects of lithium in vivo was shown by the finding that adrenalectomy partially counteracted the lithium-induced impairment of glucose tolerance and glucose-induced IRI secretion (Fontela et al, 1986). In this case, however, adrenalectomy would influence other counter-regulatory hormones, which might in turn modify the lithium response.…”

“…These effects of lithium can be counteracted by pretreatment of rats with dihydroergotamine (DHE), a non-selective a-adrenoceptor antagonist (Fontela et al, 1986;1987). a-Adrenoceptors are divided into two groups (Langer, 1974;Starke, 1977;Shattil et al, 1981).…”

Effect of lithium on plasma glucose, insulin and glucagon in normal and streptozotocin‐diabetic rats: role of glucagon in the hyperglycaemic response

“…While there have been several reports of a decrease in glucose tolerance in human patients on lithium, a similar number of studies have shown an increased tolerance; and whereas there are isolated reports of the development or deterioration of diabetes mellitus of type 1 or 2 during lithium treatment, a controlled study of type 2 diabetic patients showed a diminished plasma glucose response to a 50 g carbohydrate breakfast after 1 week of lithium administration (Jones et al, 1983). In normal rats, lithium administration causes a rise in plasma glucose while plasma insulin concentrations remain unchanged or are slightly suppressed (Fontela et al, 1986).…”

“…Glucose-stimulated insulin release is inhibited both in vivo and in vitro (Anderson & Blackard, 1978;Shah & Pishdad, 1980;Fontela et al, 1986;1987), and these effects appear to be mediated by central opiate and by neural and endocrine catecholamine pathways, the latter acting on the pancreatic P cell through its a2-adrenoceptors (Fontela et al, 1990; GarciaHermida et al, 1991). The aim of the present study was to investigate how this 'diabetogenic' effect of lithium in rats interacts with pre-existing diabetes mellitus, using streptozotocin-induced diabetes as the experimental model.…”