Abstract

Recent studies have reported that statins are associated with increased incidence of diabetes. Although several mechanisms have been proposed, the role of the kidney’s glucose metabolism upon statin treatment is still unclear. Thus, we investigated the role of pravastatin in gluconeogenesis and glycolysis. HK-2 and HepG2 cells were treated with pravastatin and cultured under either high- or normal-cholesterol conditions. In HK-2 cells treated with pravastatin under both high- and normal-cholesterol conditions, the protein expression of only pyruvate kinase isozymes L/R (PKLR) decreased in a dose-dependent manner, while the protein expression of other glucose metabolism related enzymes remained unchanged. Within the in vivo experiment, male C57BL/6 mice were fed either pravastatin-treated normal-fat diets for 2 or 4 weeks or pravastatin-treated high-fat diets for 16 weeks. Protein expression of PKLR in the kidneys from mice that consumed pravastatin-treated high-fat diets decreased significantly compared to the controls. Upon the treatments of pravastatin, only the PKLR expression decreased in lean mice. Furthermore, PKLR activity decreased significantly in the kidney after pravastatin treatments. However, there was no change in enzyme activity in the liver, suggesting that pravastatin decreased PKLR activity only in the kidney. This change may be associated with the hyperglycemic effect of statins.

Details

Title
Reduced expression of pyruvate kinase in kidney proximal tubule cells is a potential mechanism of pravastatin altered glucose metabolism
Author
Lee, Yong Pyo 1 ; Cho, Yuri 2 ; Eun Jee Kim 3 ; Lee, Hyojung 2 ; Hoon Young Choi 4 ; Hye Jin Wang 5 ; Kang, Eun Seok 5   VIAFID ORCID Logo  ; Kim, Yu Seun 6 ; Kim, Myoung Soo 7 ; Kim, Beom Seok 8 

 Department of Medicine, The Graduate School, Yonsei University, Seoul, Republic of Korea 
 The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea 
 The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea 
 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 
 Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 
 The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea 
 Department of Medicine, The Graduate School, Yonsei University, Seoul, Republic of Korea; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea 
 The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea 
Pages
1-8
Publication year
2019
Publication date
Mar 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2199870875
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.