Differential Diabetogenic Effect of Pitavastatin and Rosuvastatin, in vitro and in vivo
| Autor: | Eun Yeong Choe, Eun Seok Kang, Youjin Kim, Yongin Cho, Hyun Ki Park, Hye Jin Wang, Hyangkyu Lee, Ryeong-Hyeon Kim |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance Adipocyte Internal medicine Internal Medicine medicine Rosuvastatin Pitavastatin biology Insulin Biochemistry (medical) Glucose transporter nutritional and metabolic diseases medicine.disease Insulin receptor Endocrinology chemistry biology.protein Cardiology and Cardiovascular Medicine 030217 neurology & neurosurgery GLUT4 medicine.drug |
| Zdroj: | Journal of Atherosclerosis and Thrombosis. 27:429-440 |
| ISSN: | 1880-3873 1340-3478 |
| Popis: | 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% placebo, rosuvastatin, or pitavastatin for 12 weeks. Cultured HepG2, C2C12, and 3T3-L1 cells and visceral adipocytes 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 attenuation in insulin-induced GLUT4 translocation to the plasma membrane of adipocytes was observed in pitavastatin-treated group. Conclusion Pitavastatin showed lower diabetogenic effects than rosuvastatin in mice that may be mediated by minor attenuations in insulin signaling in adipocytes. |
| Databáze: | OpenAIRE |
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