Study of the effect of lithium on plasma glucose, insulin and glycogen in normal and streptozotocin induced diabetic rats

ABSTRACT

Lithium [Li] is used widely in different psychiatric disorders. It has variable and inconclusive effects on glucose tolerance. The objective of the study was to examine the effects of lithium on plasma glucose [G], glucagon and insulin, and their responses to IV G in male wistar rats. Plasma G, glucagon [by RIA], insulin [by RIA], and serum Li [by flame photometry] were measured before and 30 min after IV Li chloride [4 mEq/kg] in 10 normal and 10 streptozotocin induced diabetic rats [under light ether anaesthesia]. These parameters were also determined before, at 30 and 90 min following combined IV administration of Li chloride [4 mEq/kg] and G [0.5 g/kg] in 10 normal and 10 diabetic rats. In normal rats, Li injection resulted in a significant increase in mean plasma G [55%] and glucagon [91%]. This was associated with a significant drop in mean plasma insulin [71%]. Combined Li and G administration was followed by an increase in both mean plasma G [42%] and glucagon [98%]; a further elevation was observed at 90 min. The addition of G to Li failed to alter the inhibitory effect of the latter on plasma insulin which persisted till 90 min.. In diabetic rats, mean fasting plasma G and glucagon were significantly higher than those in normal rats, while mean plasma insulin was significantly lower [p < 0.001]. Administration of Li was associated with a further significant increase in plasma G and glucagon and a decrease in plasma insulin. Addition of G to Li failed to alter the responses of mean plasma G, glucagon and insulin, when compared to Li alone. These changes did not persist at 90 min as in normal rats. Serum Li levels [basal and after Li injection] were comparable in normal and diabetic rats. We conclude that acute Li administration is associated with an increase in plasma glucose in both normal and diabetic rats. This hyperglycemia is due to accelerated glucagon and diminished insulin secretion