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Differential Diabetogenic Effect of Pitavastatin and Rosuvastatin, in Vitro and in Vivo

Authors
 Yongin Cho  ;  Hyangkyu Lee  ;  Hyun Ki Park  ;  Eun Yeong Choe  ;  Hye Jin Wang  ;  Ryeong-Hyeon Kim  ;  Youjin Kim  ;  Eun Seok Kang 
Citation
 JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS, Vol.27(5) : 429-440, 2020-05 
Journal Title
 JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 
ISSN
 1340-3478 
Issue Date
2020-05
Keywords
Adipocyte ; Diabetes ; Insulin resistance ; Insulin signaling ; Pitavastatin ; Rosuvastatin
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% 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.
Files in This Item:
T202001160.pdf Download
DOI
10.5551/jat.50039
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
3. College of Nursing (간호대학) > Dept. of Nursing (간호학과) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Wang, Hye Jin(왕혜진)
Lee, Hyang Kyu(이향규) ORCID logo https://orcid.org/0000-0002-0821-6020
Cho, Yong In(조용인) ORCID logo https://orcid.org/0000-0002-4645-816X
Choe, Eun Yeong(최은영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175995
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