The Effect of Lithium on Glucose and Tolbutamide-Induced Insulin Release and Glucose Tolerance in the Intact Rat*

Abstract

The effects of lithium on stimulus-induced insulin release and glucose tolerance were examined in intact, unanesthetized, and unrestrained rats with indwelling intravascular catheters. In the first study, a 150-mg iv glucose pulse was administered at 30 min after rapid iv injection of lithium carbonate (1 meq/kg) or vehicle. After the glucose pulse, mean serum glucose levels throughout the observation period were significantly greater in the lithium-treated rats than in the vehicle-treated (control) rats. Similarly, a mean glucose disappearance rate of 2.8 +/- 0.2%/min in the lithium-treated rats was significantly less (P < 0.02) than the mean glucose disappearance rate of 3.4 +/- 0.2%/min observed in the control rats. In response to glucose pulse, acute insulin release was significantly inhibited in the lithium-treated rats compared with that observed in the control rats. In the second study, a 10-mg tolbutamide pulse was administered 30 min after a rapid iv injection of lithium carbonate or vehicle. Acute insulin release in response to tolbutamide pulse was markedly inhibited in the lithium-treated rats compared with that observed in the control rats. In lithium-treated rats, the decline in serum glucose between 10-45 min after the tolbutamide pulse was significantly less than that observed in the control rats. Therefore, in the intact rat, lithium inhibits glucose- and tolbutamide-induced insulin release, which, in turn, causes glucose intolerance and prevents tolbutamide-induced hypoglycemia.

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

“…Lithium has been shown to inhibit glucose-stimulated insulin release in the rat after either in vitro or in vivo administration, leading to impairment of glucose tolerance (Anderson & Blackard, 1978;Shah & Pishdad, 1980). 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).…”

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

“…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.…”

Endocrine disturbances related to the use of lithium

“…Studies in rats showed that intravenous infusion of lithium leads to hyperglycemia, increased levels of glucagon and lower insulin response induced by both glucose and tolbutamide (52). These effects can be attributed to the action of catecholamines in the sympathetic-adrenal system, pro-moting glycogenolysis, and to the direct effect of the drug on pancreatic alpha-2 and beta-adrenergic receptors, determining the reduction of insulin secretion and increased levels of glucagon (53).…”