Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To explore metabolic changes associated with the sorbitol accumulation and myo-inositol depletion observed in glomeruli of rats with experimental diabetes, we examined total and ouabain-inhibited adenosine triphosphatase (ATPase) activity in glomeruli isolated from control and streptozocin (STZ)-diabetic rats. Glomerular Na/K-ATPase activity (ouabain-inhibited) was significantly reduced in diabetic animals, while total (composite) ATPase activity remained unchanged. Treatment with insulin partially restored the Na/K-ATPase activity. Administration of the aldose reductase inhibitor, sorbinil, which normalizes glomerular contents of both sorbitol and myo-inositol in diabetes, completely prevented the diminution of Na/K-ATPase activity. These results establish that glomerular Na/K-ATPase activity is reduced in acute experimental diabetes. The ability of sorbinil to prevent this decrease suggests that it is related to polyol accumulation and/or myoinositol depletion, although an effect of the drug unrelated to its aldose reductase inhibiting property has not been excluded. Since increased polyol pathway flux, decreased myo-inositol, and reduced Na/K-ATPase activity have also been described in peripheral nerve, another tissue in which typical diabetic complications characteristically occur, the consequences of these metabolic changes may be implicated in the pathogenesis of diabetic nephropathy.
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PMID:Reduced glomerular sodium/potassium adenosine triphosphatase activity in acute streptozocin diabetes and its prevention by oral sorbinil. 299 80

To explore a possible link between diabetic nephropathy and the enhanced activity of the polyol pathway known to occur in diabetes, we examined several pertinent metabolic parameters in glomeruli isolated from control and streptozotocin-diabetic rats and assessed whether changes observed in diabetic glomeruli could be prevented by the oral administration of the aldose reductase inhibitor sorbinil. We found that glomerular polyol content is significantly increased in diabetes, whereas glomerular myo-inositol content is significantly reduced. The sorbitol accumulation and myo-inositol depletion were both completely prevented by sorbinil, which was given throughout the duration of diabetes. Activity of the membrane-bound sodium/potassium adenosine triphosphatase (Na-K-ATPase) was decreased in diabetic samples; this change was also completely prevented by sorbinil. Erythrocyte deformability is another factor that has been implicated in the pathogenesis of microangiopathic complications. The ability of red blood cells to undergo an adaptation in shape that permits passage through the smallest vessels is impaired in diabetes. Using blood from control, diabetic, and sorbinil-treated diabetic rats, we found that erythrocyte deformability was decreased in diabetic samples and that sorbinil treatment significantly improved this parameter. Thus, if the glomerular consequences of sorbitol accumulation, myo-inositol depletion, reduced Na-K-ATPase activity, and decreased erythrocyte deformability are pathogenetically implicated in diabetic nephropathy, the ability of sorbinil to impact on these changes suggests that it could favorably impact on the nephropathic process.
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PMID:Aldose reductase, glomerular metabolism, and diabetic nephropathy. 300 26

Diabetes mellitus induces a decrease in sodium potassium-adenosine triphosphatase (Na+/K(+)-ATPase) activity in several tissues in the rat and red blood cells (RBC) and nervous tissue in human patients. This decrease in Na+/K(+)-ATPase activity is thought to play a role in the development of long-term complications of the disease. Angiotensin enzyme inhibitors (ACEi) and angiotensin-II receptor antagonists (ARBs) reduce proteinuria and retard the progression of renal failure in patients with IDDM and diabetic rats. We investigated the effects of captopril and losartan, which are used in the treatment of diabetic nephropathy, on Na+/K(+)-ATPase activity. Captopril had an inhibitory effect on red cell plasma membrane Na+/K+ ATPase activity, but losartan did not. Our study draws attention to the inhibitory effect of captopril on Na+/K+ ATPase activity. Micro and macro vascular complications are preceeding mortality and morbidity causes in diabetes mellitus. There is a strong relationship between the decrease in Na+/K+ ATPase activity and hypertension. The non-sulphydryl containing ACEi and ARBs must be the choice of treatment in hypertensive diabetic patients and diabetic nephropathy.
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PMID:The effects of captopril and losartan on erythrocyte membrane Na+/K(+)-ATPase activity in experimental diabetes mellitus. 1751 48