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

Abstract

1 Lithium salts, used in the treatment of affective disorders, may have adverse effects on glucose tolerance in man, and suppress glucose-stimulated insulin secretion in rats. 2 To study the interaction of these effects with pre-existing diabetes mellitus, plasma glucose and insulin responses to lithium chloride were measured in male Wistar rats made diabetic with intraperitoneal streptozotocin, and in normal controls. 3 In both normal and diabetic anaesthetized rats, intravenous lithium (4 mEq kg-') caused a rise in plasma glucose. In absolute terms, the rise was greater in diabetic (5.2 mmol l ) than in normal rats (2.3 mmol I`).4 Plasma insulin concentrations were reduced by lithium in normal rats, but the low insulin concentrations measured in the diabetic rats were not significantly changed. 5 After intravenous glucose (0.5 g kg-'), lithium-treated diabetic rats showed a second rise in plasma glucose at 60-90 min without any insulin response, while normal rats showed typically reduced insulin responses and initial glucose disappearance rates. 6 Intravenous glucose reduced plasma glucagon concentrations to a greater extent in normal than in diabetic rats, but lithium induced an equal rise in plasma glucagon in both groups, with a time-course similar to that of the hyperglycaemic effect. 7 The hyperglycaemic action of lithium is greater in the hypoinsulinaemic diabetic rats and appears to involve a stimulation of glucagon secretion in both normal and diabetic animals.

Could Selenium Administration Alleviate the Disturbances of Blood Parameters Caused by Lithium Administration in Rats?

“…It is a very important result considering the relationships between lithium and enzymes involved in glucose metabolism [ 29 , 31 , 32 ]. Intravenous lithium was reported to cause an increase in plasma glucose and depletion of plasma insulin in normal rats [ 33 ]. Studies also revealed the occurrence of hyperglycaemia as one of the metabolic disturbances noted in bipolar disorder patients [ 34 ].…”

Mechanism and Management of AKT Inhibitor-Induced Hyperglycemia

“…Treatment with lithium chloride, a low millimolar GSK-3 inhibitor, showed little or no effect on GSK690693-induced hyperglycemia (data not shown), suggesting that inhibition of GSK-3 alone cannot shut off the GSK690693-induced glycogenolysis owing to the fact that protein kinase A and C and many other enzymes were also shown to be involved in glycogen metabolism (35). In addition, despite the ability of lithium to restore insulin sensitivity in skeletal muscle (36), lithium can also reciprocally suppress plasma insulin and elevate glucagon secretion (37). As such, lithium exerts its effect through a combination of several biochemical properties, some of which are likely antagonized by the AKT inhibitor.…”

Manic/Hypomanic Symptom Burden and Cardiovascular Mortality in Bipolar Disorder

“…Lithium is associated with significant weight gain (43, 44). It has not been clearly associated with diabetes mellitus or insulin resistance in clinical samples (45), however, it has insulin-like physiological effects (46, 47) and may increase plasma glucose in animal models (48). Valproic acid derivatives have long-been associated with insulin resistance and weight gain (49, 50) while carbamazepine has been associated with hyperlipidemia (51).…”