Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat

Morris, R. Curtis; Nigon, Kathleen; Reed, Elizabeth B.

doi:10.1172/jci108920

Cited by 77 publications

(38 citation statements)

References 49 publications

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“…Fructose is phosphorylated to fructose-1-phosphate by fructokinase, which uses ATP in the phosphorylation leading to generation of AMP and activation of AMP deaminase (Mäenpää PH et al, 1968). The activation of AMP deaminase leads to enhancement of the production of uric acid (Perheentupa and Raivio, 1967;Morris et al, 1978). This is evidenced by the results of a study, in which serum uric acid levels were increased rapidly after ingestion of fructose in humans (Perheentupa and Raivio, 1967).…”

Section: D a B E Fmentioning

confidence: 95%

High fructose diet feeding accelerates diabetic nephropathy in Spontaneously Diabetic Torii (SDT) rats

et al. 2018

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-Diabetic nephropathy (DN) is one of the complications of diabetes and is now the most common cause of end-stage renal disease. Fructose is a simple carbohydrate that is present in fruits and honey and is used as a sweetener because of its sweet taste. Fructose has been reported to have the potential to progress diabetes and DN in humans even though fructose itself does not increase postprandial plasma glucose levels. In this study, we investigated the effects of high fructose intake on the kidney of the Spontaneously Diabetic Torii (SDT) rats which have renal lesions similar to those in DN patients and compared these with the effects in normal SD rats. This study revealed that a 4-week feeding of the high fructose diet increased urinary excretion of kidney injury makers for tubular injury and accelerated mainly renal tubular and interstitial lesions in the SDT rats but not in normal rats. The progression of the nephropathy in the SDT rats was considered to be related to increased internal uric acid and blood glucose levels due to the high fructose intake. In conclusion, high fructose intake exaggerated the renal lesions in the SDT rats probably due to effects on the tubules and interstitium through metabolic implications for uric acid and glucose.

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Section: D a B E Fmentioning

confidence: 95%

High fructose diet feeding accelerates diabetic nephropathy in Spontaneously Diabetic Torii (SDT) rats

et al. 2018

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“…36,37 This process has been usually studied in the liver; however, KHK is highly expressed in HK-2 cells and fructose-induced MCP-1 and ROS production might be suppressed by XOR inhibition. We therefore examined the expression of XOR in HK-2 cells and measured uric acid, the XOR reaction product.…”

Section: Xor Expression and Uric Acid Production In Response To Fructmentioning

confidence: 99%

Ketohexokinase-Dependent Metabolism of Fructose Induces Proinflammatory Mediators in Proximal Tubular Cells

Cirillo

Gersch

et al. 2009

Journal of the American Society of Nephrology

243

215

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Increased consumption of fructose may play an important role in the epidemic of metabolic syndrome and may presage the development of diabetes, cardiovascular disease, and chronic kidney disease. Once in the cell, fructose is phosphorylated by ketohexokinase (KHK), leading to consumption of ATP, formation of AMP, and generation of uric acid through xanthine oxidoreductase (XOR). This study aimed to examine the direct effects of fructose in human kidney proximal tubular cells (HK-2) and whether they are mediated by the fructose metabolism via KHK. At a similar concentration to that observed in peripheral blood after a meal, fructose induced production of monocyte chemotactic protein 1 (MCP-1) and reactive oxygen species in HK-2 cells. Knockdown of KHK by stable transfection with small hairpin RNA demonstrated that these processes were KHK dependent. Several antioxidants, including specific inhibitors of NADPH oxidase and XOR, prevented MCP-1 secretion. We detected XOR mRNA in HK-2 cells and confirmed its activity by identifying uric acid by mass spectrometry. Fructose increased intracellular uric acid, and uric acid induced production of MCP-1 as well. In summary, postprandial concentrations of fructose stimulate redox-and urate-dependent inflammatory mediators in proximal tubular cells.

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“…If cytosolic Pi is reduced sufficiently, the rates of glycolysis and oxygen consumption are inhibited. Similarly, intracellular Pi and ATP are reduced in rat liver and kidney cells exposed to fructose (7)(8)(9). These observations suggest that the incorporation of Pi into glycolytic substrates may limit the availability of Pi for oxidative phosphorylation (6).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Requirement for Inorganic Phosphate by the Rabbit Proximal Tubule

Brazy¹,

Gullans²,

Mandel³

et al. 1982

J. Clin. Invest.

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A B S T R A C T These studies examine the effects of acute changes in the availability of inorganic phosphate on the function of isolated proximal renal tubules from rabbit kidney. We removed phosphate from the extracellular fluids and measured fluid absorption rates in isolated. perfused tubules and oxygen consumption rates in suspensions of cortical tubules. In proximal convoluted tubules, the selective removal of phosphate from the luminal fluid reduced fluid absorption rates from 1.11±0.12 to -0.01±0.08 nl/mmmin. This effect on fluid absorption was dependent on the presence of glucose transport and metabolism. The addition of phlorizin to the phosphate-free luminal fluid preserved fluid absorption rates (1.12±0.12 nl/ mm -min) as did the substitution of nonmetabolized a-methyl D-glucopyranoside for glucose (1.05±0.21 nl/mm min) or the addition of 2-deoxyglucose, an inhibitor of glycolysis, to the bathing medium (1.01±0.15 nl/mm -min). There was no effect on fluid absorption if phosphate was removed from the bath only. Additionally, removal of phosphate from the luminal fluid of proximal straight rather than convoluted tubules had no effect on fluid absorption rates. Oxygen consumption rates in suspensions of cortical tubules were reduced from 18.9±0.6 to 10.6±0.6 nmol O2/mg tubular protein * min by the removal of phosphate from the medium. This inhibition was prevented by the substitution of a-methyl D-glucopyranoside for glucose in the phosphate-free medium. The data indicate that under certain conditions, proximal convoluted tubules require the presence of phosphate in the luminal fluid to preserve tubular function. In the absence of intraluminal phosphate, glucose metabolism causes a reduction in both oxidative metab-

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Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat

Cited by 77 publications

References 49 publications

High fructose diet feeding accelerates diabetic nephropathy in Spontaneously Diabetic Torii (SDT) rats

High fructose diet feeding accelerates diabetic nephropathy in Spontaneously Diabetic Torii (SDT) rats

Ketohexokinase-Dependent Metabolism of Fructose Induces Proinflammatory Mediators in Proximal Tubular Cells

Metabolic Requirement for Inorganic Phosphate by the Rabbit Proximal Tubule

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