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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.
This article was published in the following journal.
Name: Scientific reports
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The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE.
Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER.
The U-shaped portion of the renal tubule in the KIDNEY MEDULLA, consisting of a descending limb and an ascending limb. It is situated between the PROXIMAL KIDNEY TUBULE and the DISTAL KIDNEY TUBULE.
A double-walled epithelial capsule that is the bulbous closed proximal end of the kidney tubular system. It surrounds the cluster of convoluted capillaries of KIDNEY GLOMERULUS and is continuous with the convoluted PROXIMAL KIDNEY TUBULE.
A hereditary or acquired form of generalized dysfunction of the PROXIMAL KIDNEY TUBULE without primary involvement of the KIDNEY GLOMERULUS. It is usually characterized by the tubular wasting of nutrients and salts (GLUCOSE; AMINO ACIDS; PHOSPHATES; and BICARBONATES) resulting in HYPOKALEMIA; ACIDOSIS; HYPERCALCIURIA; and PROTEINURIA.
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