Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous digital-like substance (DLS) is increased in patients with essential hypertension and is hypothesized to play a role in the pathogenesis of high blood pressure. Whether an increase in DLS in diabetic patients with hypertension is associated with a family history of hypertension or diabetic nephropathy was investigated. Plasma DLS was measured as Na(+)-K(+)-ATPase inhibitory activity (ATPI) in 100 Type 2 diabetic patients. Ouabain was used as a standard of Na-K-ATPase inhibition. Diabetic patients with hypertension demonstrated a greater ATPI level than normotensive diabetic patients (p less than 0.05). In patients with hypertension groups, the positive family history group had a higher ATPI level than the negative family history group (p less than 0.01). Microalbuminuria was not correlated with the ATPI level in diabetic patients. These results suggest that ATPI might play a role in the pathogenesis of hereditary hypertension associated with diabetes mellitus, but not have etiologic significance in diabetic nephropathy.
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PMID:Elevated endogenous digitalis-like substance in hypertensive diabetic patients with a family history of hypertension. 165 64

Digitalis-like substance (DLS) was measured by Na-K-ATPase inhibitor (ATPI) activity and digitalis-like immunoreactivity (DLI) in 100 patients with type II diabetes. Hypertensive diabetic patients with a positive family history for hypertension had high ATPI levels compared with those patients with a negative family history for the disease. DLI level did not differ between groups. There was no significant difference in ATPI and DLI levels among three groups based on level of urinary albumin excretion. These data suggest that a circulating factor (or circulating factors) determined by ATPI may be linked with genetic factors in the development of hypertension, but not to the development of diabetic nephropathy.
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PMID:Elevated endogenous Na-K-ATPase inhibitor activity in hypertensive diabetic patients with a family history of hypertension. 166 15

The progression of diabetic nephropathy can be arrested by an improvement in diabetic control. High glucose concentrations increase the flux through the aldose reductase pathway, and it has been proposed that this may contribute to renal damage. Aldose reductase is present in both the glomerulus and the renal tubule. Biochemical changes associated with increased sorbitol production have been demonstrated in animal models, including myo-inositol depletion, reduced Na+-K+ ATPase activity, and activation of the pentose phosphate and glucuronate-xylose pathways. Selective inhibition of aldose reductase reverses these biochemical changes and prevents some of the structural and functional abnormalities in diabetic rats. The potential beneficial effects of aldose reductase inhibitors on diabetic kidney disease in man are at present being investigated.
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PMID:Aldose reductase in the etiology of diabetic complications: 2. Nephropathy. 252 43

Alterations in ouabain inhibitable Na-K ATPase activity, polyol pathway activity, and myoinositol metabolism are part of a unifying hypothesis proposed to explain the pathogenesis of the chronic complications of diabetes mellitus. Direct measurements of renal ouabain inhibitable Na-K ATPase activity in animals with streptozotocin-induced diabetes show increased or decreased activity, depending on the nephron segment examined and the duration of diabetes. While myoinositol feeding corrects depressed Na-K ATPase activity in peripheral nerve of streptozotocin diabetic rats, the effect of myoinositol feeding on altered renal Na-K ATPase activity is unknown. To assess the effect of experimental diabetes on renal ouabain inhibitable Na-K ATPase activity and test the involvement of the polyol/inositol pathway, we assayed kidneys from normal, streptozotocin diabetic, and myoinositol-supplemented diabetic rats for renal ouabain-inhibitable Na-K ATPase, alkaline phosphatase, and tau-glutamyltranspeptidase (tau-GT) activity. Ouabain inhibitable Na-K ATPase activity, expressed per milligram of protein, is increased in the inner medulla of the diabetic kidney compared with normal and, expressed per microgram DNA, is increased in both the inner medulla and cortex. Myoinositol supplementation did not affect the increase in renal enzyme activity seen with streptozotocin diabetes. These observations suggest that the regulation of renal ouabain inhibitable Na-K ATPase activity, in streptozotocin diabetes, does not depend on supplemental myoinositol. These findings do not exclude the possibility that changes in polyol or myoinositol concentrations in a specific nephron segment may have pathogenetic significance for diabetic nephropathy.
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PMID:Renal ouabain inhibitable Na-K ATPase activity and myoinositol supplementation in experimental diabetes mellitus. 289 13

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

A lower concentration of intracellular myo-inositol has been implicated in the development of diabetic nephropathy. This was based on short-term studies showing that early administration of aldose reductase inhibitors or myo-inositol supplementation reduces increased glomerular filtration rate and partly reduces increased urinary albumin excretion in streptozotocin diabetic rats. We studied the effect of long-term (4 months) administration of 1% myo-inositol supplement to the Cohen diabetic (type 2) rat on the development of nephropathy and renal Na(+)-K(+)-ATPase. This treatment reduced the increased renal Na(+)-K(+)-ATPase activity but had no effect on blood glucose levels, body weight, increased kidney weight, or creatinine clearance and did not prevent or reduce the development of renal glomerular pathology. There was no correlation between the level of Na(+)-K(+)-ATPase activity and the degree of nephropathy. It is possible that the renal pathological changes are due to metabolic and humoral factors resulting from hyperglycaemia, other than myo-inositol depletion. The fact that myo-inositol treatment had no effect on the development of renal pathological changes but was shown to have a beneficial effect on restoring impaired conduction velocity and on the disruption of structural elements in the nerve indicates that the effect of the biological changes ensuing from hyperglycaemia vary in different tissues depending on local conditions.
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PMID:Effect of myo-inositol supplementation on the development of renal pathological changes in the Cohen diabetic (type 2) rat. 758 74

Increased erythrocyte sodium-lithium countertransport activity has been implicated in the pathogenesis of diabetic nephropathy. However, its relationship to other cation membrane transport systems in incipient nephropathy is not yet clear. The present study was thus performed to: (1) explore associations between sodium-lithium countertransport and changes in the activity of other cation transport pathways and (2) to compare the sodium transport activities with clinical characteristics of insulin-dependent diabetic patients with and without evidence of incipient diabetic nephropathy. We measured erythrocyte sodium-lithium countertransport, passive sodium/potassium flux (at 1 degree C), adenine nucleotide content in intact erythrocytes and sodium/potassium-, magnesium- and calcium-dependent ATPase activity in erythrocyte membrane preparations from 34 insulin-dependent diabetic patients without microalbuminuria, 8 diabetic patients with microalbuminuria, and 8 age-matched healthy control subjects. Sodium-lithium countertransport was elevated in diabetic patients with normo- and microalbuminuria compared with control subjects [268 +/- 99 and 299(277-465), respectively, vs. 166 +/- 65 mumol/(1 cells x h)] and was positively correlated (r = 0.36, P < 0.05) with the albumin excretion rate. However, the activity of erythrocyte membrane ATPases was significantly decreased compared with control subjects. The ATP and ADP content was found to be significantly higher (P < 0.001) in erythrocytes from diabetic patients compared with control subjects (1,196 +/- 276 vs. 833 +/- 253 mumol/l cells and 353 +/- 97 vs. 255 +/- 64 mumol/l cells, respectively). The extent of erythrocyte potassium leakage correlated with hemoglobin A1c (r = 0.39, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Erythrocyte sodium-lithium countertransport, adenosine triphosphatase activity and sodium-potassium fluxes in insulin-dependent diabetes. 766 4

In order to elucidate the causal relationship between (Na(+)-K+)ATPase and diabetic nephropathy, we studied the erythrocyte (Na(+)-K+)ATPase activity in Type 2 diabetic patients, 20 with microalbuminuria and 27 without microalbuminuria and in 16 control subjects. (Na(+)-K+)ATPase activities in microalbuminuric patients (0.273 +/- 0.012 mumol Pi/mg protein/h, mean +/- SE) were significantly reduced compared with those without microalbuminuric patients (0.308 +/- 0.011 mumol Pi/mg protein/h, p < 0.05) and control subjects (0.330 +/- 0.011 mumol Pi/mg protein/h, p < 0.01). Microalbuminuric patients had higher systolic blood pressure (133 +/- 3 vs 124 +/- 3 mmHg, p < 0.05) and greater frequency of parental hypertension (50% vs 19%, p < 0.05) than those without microalbuminuria. (Na(+)-K+)ATPase activities in diabetic patients with hypertension were significantly reduced compared with those in diabetic patients without hypertension. Moreover, (Na(+)-K+)ATPase activities in diabetic patients with parental hypertension were significantly reduced compared with those in patients without parental hypertension. There was no difference in erythrocyte Na+ content between with and without microalbuminuria or hypertension or parental hypertension in diabetic patients. Erythrocyte Na+ content was significantly negatively correlated with (Na(+)-K+)ATPase activity in control subjects (r = -0.619, p < 0.05), but not in diabetic patients (r = -0.194). Plasma digitalis-like substances showed no correlation with (Na(+)-K+)ATPase activities in diabetic patients with microalbuminuria or hypertension or parental hypertension. We concluded that the reduction of erythrocyte (Na(+)-K+)ATPase activity may be related to a familial predisposition to arterial hypertension and may partly be responsible for the development of diabetic nephropathy in Type 2 diabetic patients.
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PMID:Reduction of erythrocyte (Na(+)-K+)ATPase activity in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria. 815 Apr 21

The effects of feeding a 1% corn oil-9% menhaden oil or beef tallow diet on the early phase of diabetic nephropathy in BHE/cdb rats was studied. The diet groups were subdivided into rats with or without impaired glucose tolerance. Those fed menhaden oil had renal hypertrophy, mild albuminuria, decreased creatinine clearance, increased urea clearance, and more severe lesion scores than rats fed beef tallow. No differences in glomerular filtration rate, Na+, K+-ATPase activity, sorbitol dehydrogenase, or inositol 1, 4, 5-phosphate were observed. Beef tallow-fed rats had higher serum triglyceride levels and renal cholesterol levels. Renal and hepatic fatty acid profiles reflected the fatty acid profile of the dietary fat. These results suggest that beef tallow conferred a protective effect on the renal tissues of these diabetes-prone rats.
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PMID:Early renal disease in BHE/cdb rats is less in rats fed beef tallow than in rats fed menhaden oil. 850 57

A series of experiments were conducted to determine whether the feeding of beef tallow compared with menhaden oil would affect renal cortex membrane composition, Na,K-ATPase activity, renal cholesterol uptake, and plasma lipoprotein cholesterol profile. BHE/cdb rats were used because they carry a genetic trait for non-insulin-dependent diabetes mellitus and are prone to develop diabetic nephropathy. Beef tallow feeding resulted in an increase in HDL cholesterol and an increase in Na,K-ATPase activity. The different fats also affected the arachidonic acid content of the membrane but not the membrane cholesterol content. These diet effects may explain why the development of renal disease in beef tallow-fed rats is delayed when compared with rats fed an equivalent amount of menhaden oil.
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PMID:Differential hepatic and renal cholesterol levels in diabetes-prone BHE/cdb rats fed menhaden oil or beef tallow. 911 25


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