Differential diabetogenic effect of pitavastatin and rosuvastatin, in vitro and in vivo

Abstract

Aim: Most statins increase the risk of new-onset diabetes. Unlike other statins, pitavastatin is reported to exert neutral effects on serum glucose level, but the precise mechanism is unknown. Methods: Eight-week-old male C57BL/6J mice (n=26) were fed high-fat diet (HFD, 45% fat) with 0.01% pla-cebo, rosuvastatin, or pitavastatin for 12 weeks. Cultured HepG2, C2C12, and 3T3-L1 cells and visceral adipo-cytes from HFD-fed mice were treated with vehicle or 10 µM statins for 24 h. The effects of pitavastatin and rosuvastatin on intracellular insulin signaling and glucose transporter 4 (GLUT4) translocation were evaluated. Results: After 12 weeks, the fasting blood glucose level was significantly lower in pitavastatin-treated group than in rosuvastatin-treated group (115.2±7.0 versus 137.4±22.3 mg/dL, p=0.024). Insulin tolerance significantly improved in pitavastatin-treated group as compared with rosuvastatin-treated group, and no significant difference was observed in glucose tolerance. Although plasma adiponectin and insulin levels were not different between the two statin treatment groups, the insulin-induced protein kinase B phosphorylation was weakly attenuated in pitavastatin-treated adipocytes than in rosuvastatin-treated adipocytes. Furthermore, minor attenu-ation in insulin-induced GLUT4 translocation to the plasma membrane of adipocytes was observed in pitavas-tatin-treated group. Conclusion: Pitavastatin showed lower diabetogenic effects than rosuvastatin in mice that may be mediated by minor attenuations in insulin signaling in adipocytes.