Treatment with atorvastatin attenuates progression of insulin resistance and pancreatic fibrosis in the Otsuka Long-Evans Tokushima fatty rats.

Abstract Purpose The effects of statins on insulin resistance (IR) and type 2 diabetes mellitus (T2DM) are still controversial and its effects on pancreatic fibrosis are poorly defined. The purpose of this study is to examine the effects of atorvastatin on these issues using the Otsuka Long–Evans Tokushima Fatty (OLETF) rat, an animal model of IR, T2DM and pancreatic fibrosis. Methods Male OLETF rats were divided into 2 groups at 6 weeks of age. The first group received a standard diet until the end of experimental period at age 28 weeks. The second group was given a diet containing 0.05% atorvastatin from 6 weeks of age, before the onset of IR and pancreatic fibrosis. The age-matched Long–Evans Tokushima Otsuka rats without presence of IR, T2DM and pancreatic fibrosis, received a standard diet and were used as a normal control. Results Atorvastatin slightly decreased serum fasting glucose and insulin levels, but significantly improved index of IR compared with the untreated OLETF rats. In addition, atorvastatin markedly decreased transforming growth factor-β1 mRNA expression, myeloperoxidase activity and proportion of fibrotic area, and elevated superoxide dismutase activity in the pancreas compared with the untreated OLETF rats. Conclusions These findings suggest that atorvastatin exerts favorable influence on progression of IR and pancreatic inflammation and fibrosis via pleiotropic effect such as anti-oxidative property.