Reduced expression of pyruvate kinase in kidney proximal tubule cells is a potential mechanism of pravastatin altered glucose metabolism

Yong Pyo Lee, Yuri Cho, Eun Jee Kim, Hyojung Lee, Hoon Young Choi, Hye Jin Wang, Eun Seok Kang, YuSeun Kim, Myoung Soo Kim, Beom Seok Kim

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number5318
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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Pravastatin
Proximal Kidney Tubule
Pyruvate Kinase
Glucose
Isoenzymes
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Kidney
High Fat Diet
Cholesterol
Proteins
Gluconeogenesis
Hep G2 Cells
Glycolysis
Enzymes
Inbred C57BL Mouse
Fats
Diet

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lee, Yong Pyo ; Cho, Yuri ; Kim, Eun Jee ; Lee, Hyojung ; Choi, Hoon Young ; Wang, Hye Jin ; Kang, Eun Seok ; Kim, YuSeun ; Kim, Myoung Soo ; Kim, Beom Seok. / Reduced expression of pyruvate kinase in kidney proximal tubule cells is a potential mechanism of pravastatin altered glucose metabolism. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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Reduced expression of pyruvate kinase in kidney proximal tubule cells is a potential mechanism of pravastatin altered glucose metabolism. / Lee, Yong Pyo; Cho, Yuri; Kim, Eun Jee; Lee, Hyojung; Choi, Hoon Young; Wang, Hye Jin; Kang, Eun Seok; Kim, YuSeun; Kim, Myoung Soo; Kim, Beom Seok.

In: Scientific reports, Vol. 9, No. 1, 5318, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Choi, Hoon Young

AU - Wang, Hye Jin

AU - Kang, Eun Seok

AU - Kim, YuSeun

AU - Kim, Myoung Soo

AU - Kim, Beom Seok

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