Antidiabetic and vasoprotective activity of lithium: Role of glycogen synthase kinase-3

Lithium is a drug of choice in maniac disorder. Lithium inhibits the glycogen synthase kinase-3 (GSK-3), an enzyme involved in the insulin signalling pathway. Elevated levels of GSK-3 were found in diabetic rats and humans. We aimed to determine the effect of lithium chloride in diabetes and associated vascular complications in diabetic rats.

Type 2 diabetes was induced by high fat diet and low dose of streptozotocin. Diabetic rats were divided into diabetic control and lithium chloride treatment groups. Lithium chloride was used as a GSK-3 inhibitor. The treatment was given for 4 weeks. Various biochemical parameters were measured before initiation and the end of treatment. Systolic blood pressure was measured by the non-invasive tail-cuff method, while various biochemical and tissue parameters were estimated for efficacy. Vasoreactivity was performed by taking the contractile response of H(2)O(2) (10(-6) M to 10(-3)M) and angiotensin II (10(-11) to 10(-7) M) in rat thoracic aortas of different groups. Statistical comparisons between all groups were performed by using two tailed one-way ANOVA followed by the Dunnett test. P-values <0.05 were considered statistically significant.

Treatment with lithium chloride significantly reduced the augmented systolic blood pressure, various biochemical parameters, and antioxidant parameters in diabetic-treated rats. Treatment also showed the decrease in augmented responses of H(2)O(2) and angiotensin II in rat thoracic aortas of treated rats.

We can conclude that lithium chloride treatment reduces the diabetic state as well as diabetes-induced vascular dysfunction.