Differential Diabetogenic Effect of Pitavastatin and Rosuvastatin, <i>in vitro</i> and <i>in vivo </i>
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- Cho Yongin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine
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- Lee Hyangkyu
- Yonsei University College of Nursing, Mo-Im Kim Nursing Research Institute, Biobehavioral Research Center
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- Park Hyun Ki
- Yonsei University College of Nursing, Mo-Im Kim Nursing Research Institute, Biobehavioral Research Center
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- Choe Eun Yeong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine
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- Wang Hye Jin
- Brain Korea 21 PLUS Project for Medical Science; Yonsei University College of Medicine
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- Kim Ryeong-Hyeon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine
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- Kim Youjin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine
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- Kang Eun Seok
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine Brain Korea 21 PLUS Project for Medical Science; Yonsei University College of Medicine
抄録
<p>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. </p><p>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. </p><p>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. </p><p>Conclusion: Pitavastatin showed lower diabetogenic effects than rosuvastatin in mice that may be mediated by minor attenuations in insulin signaling in adipocytes.</p>
収録刊行物
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- Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ
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Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ 27 (5), 429-440, 2020-05-01
一般社団法人 日本動脈硬化学会