EFFECT OF LITHIUM ON PLASMA-GLUCOSE, INSULIN AND GLUCAGON IN NORMAL AND STREPTOZOTOCIN-DIABETIC RATS - ROLE OF GLUCAGON IN THE HYPERGLYCEMIC RESPONSE

1 Lithium salts, used in the treatment of affective disorders, may hav e adverse effects on glucose tolerance in man, and suppress glucose-st imulated insulin secretion in rats. 2 To study the interaction of thes e effects with pre-existing diabetes mellitus, plasma glucose and insu lin responses to lithium chloride were measured in male Wistar rats ma de diabetic with intraperitoneal streptozotocin, and in normal control s. 3 In both normal and diabetic anaesthetized rats, intravenous lithi um (4 mEq kg(-1)) caused a rise in plasma glucose. In absolute terms, the rise was greater in diabetic (5.2 mmol 1(-1)) than in normal rats (2.3 mmol 1(-1)). 4 Plasma insulin concentrations were reduced by lith ium in normal rats, but the low insulin concentrations measured in the diabetic rats were not significantly changed. 5 After intravenous glu cose (0.5 g kg(-1)), lithium-treated diabetic rats showed a second ris e in plasma glucose at 60-90 min without any insulin response, while n ormal rats showed typically reduced insulin responses and initial gluc ose disappearance fates. 6 Intravenous glucose reduced plasma glucagon concentrations to a greater extent in normal than in diabetic rats, b ut lithium induced an equal rise in plasma glucagon in both groups, wi th a time-course similar to that of the hyperglycaemic effect. 7 The h yperglycaemic action of lithium is greater in the hypoinsulinaemic dia betic rats and appears to involve a stimulation of glucagon secretion in both normal and diabetic animals.