Insulin resistance plays an important role not only in the development and progression of diabetes mellitus but also in the establishment of metabolic syndrome. Improvement of insulin resistance is thus of great importance both in improving glucose metabolism and preventing atherosclerosis. Although HMG-CoA reductase inhibitors appear to favorably affect glucose metabolism, as indicated by the results of a subanalysis in the West of Scotland Coronary Prevention Study (WOSCOPS), their effects on glucose metabolism and insulin resistance have not been thoroughly investigated in animal models. In this study, the effects of atorvastatin on the glucose metabolism and insulin resistance of KK/Ay mice, an animal model of type II diabetes, were investigated. Atorvastatin significantly decreased the non-HDL-cholesterol level in the oral glucose tolerance test, inhibited increase in the 30-min glucose level, decreased plasma insulin levels before and 30 and 60 minutes after glucose loading, and decreased the insulin resistance index, compared with corresponding values in controls, indicating that atorvastatin appeared to improve glucose metabolism by improving insulin resistance. Northern blot analysis revealed decreases in levels of mRNA of sterol regulatory element binding protein-1 (SREBP-1) and glucose-6-phosphatase (G6Pase), and it may play a role in the improvement of glucose metabolism and insulin resistance.
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