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

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: We can conclude that lithium chloride treatment reduces the diabetic state as well as diabetes-induced vascular dysfunction.