Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The evidence of sorbitol excess in the crystalline lens of alloxan-diabetic rats has led to anticipate the role of the enzyme aldose-reductase in the pathogenesis of the diabetic cataract. In addition, a number of experimental works have more recently shown the involvement of myoinositol deficiency, which probably results from the sorbitol accumulation. These metabolic pathways are most likely implicated in the pathogenesis of diabetic neuropathy and perhaps additionally in that of microangiopathy. The synthesis of several aldose-reductase inhibitors (AR inhibitors) confirmed experimentally these hypothesis. By reducing the activity of the enzyme aldose-reductase, these substances suppress the adverse metabolic consequences of polyol accumulation, myositol deficiency and dysfunction of the Na+/K+ ATPase dependent sodium activity. Although different experimentations showed that the AR inhibitors could prevent in animals the development of experimental cataract as well as the early functional or later anatomic abnormalities of the diabetic retinopathy and nephropathy, the clinical trials did not clearly support these experimental results in humans. On the other hand, the AR inhibitors were proved to exhibit some efficacy in the early stage of diabetic neuropathy and in incipient nephropathy where they delay the development of albustix positive proteinuria. However, the benefit of an early treatment with AR inhibitors should be confirmed by long term prospective studies, which could also assess the safety of these drugs in chronic administration.
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PMID:[Role of polyols in the development of diabetic complications. Value of aldose-reductase inhibitors]. 141 Aug 79

Thirty-six male Lewis rats rendered diabetic using alloxan received syngeneic pancreaticoduodenal grafts. Seven days prior to and 7, 30, and 90 days posttransplantation, the animals were housed in metabolic cages for periods of 48 hours. During this time, body weight, water intake, food intake, urine output, and fecal output were recorded every 24 hours. Blood sugar, plasma insulin, glucosuria, and proteinuria were determined at 3-month intervals prior to the transplant and at monthly intervals posttransplantation. These parameters were also concurrently recorded for diabetic control rats. Pancreaticoduodenal transplantation produces immediate relief of hyperglycemia, glucosuria, polyuria, polyphasia, and polydypsia, resulting in good health of the animals until the time of sacrifice. A significantly increased insulin level was also recorded. The transplanted animals showed a weight gain reflecting that of a normal growth curve.
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PMID:Metabolic effect of pancreas transplantation on long-term diabetic rats. 219 25

The relationship between urinary protein excretion and control of diabetes was evaluated in alloxan-diabetic dogs prospectively assigned to poor, moderate, or good glycaemic control. Protein excretion rate increased with the duration of insulin deficiency, and was significantly greater than normal in the poor control group by the fourth year of diabetes. Appreciable differences in the severity of the proteinuria were observed among animals of the poor and moderate glycaemic control groups; some of the animals excreted in excess of 500 mg protein/24 h while others excreted no more than normal throughout the 5 years of study. Differences in glycaemic control among these insulin-deficient animals seem not sufficient to account for the observed differences in protein excretion. Immunoassay for albumin indicated that the defect resulting in supranormal protein excretion was at least partly glomerular in origin. Good glycaemic control prevented the protein loss from exceeding normal. A potential role of hyperglycaemia in the development of proteinuria was examined in nondiabetic dogs made experimentally hyperglycaemic with galactose. Consumption of a 30% galactose diet for up to 5 years duration had little influence on protein excretion.
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PMID:Urinary protein excretion rates in experimentally diabetic dogs and experimentally galactosaemic dogs. 324 Aug 45

The uptake of magnesium-28 was measured in slices of kidney cortex from rats with alloxan-diabetes and from rats with streptozotocin-diabetes of increasing durations. In both forms of chemically-induced diabetes, magnesium-28 uptake by kidney cortex slices was significantly increased over uptake measured in kidney cortex slices from control rats. Immediate institution of daily insulin therapy to the diabetic rats prevented the diabetes-induced elevated uptake of magnesium without controlling blood glucose levels. Late institution of daily insulin therapy was ineffective in restoring the magnesium uptake to control values. These alterations in magnesium uptake occurred prior to any evidence of nephropathy (via the classic indices of proteinuria and increased BUN levels). The implications of these findings, together with our earlier demonstrations of altered calcium transport by kidney cortex slices from chemically-induced diabetic rats, are discussed in terms of disordered divalent cation transport being at least part of the basic pathogenesis underlying diabetic nephropathy.
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PMID:Altered magnesium transport in slices of kidney cortex from chemically-induced diabetic rats. 703 10

We previously reported the renal hemodynamic effects of different antihypertensive regimens in uninephrectomized, alloxan-induced, diabetic (DM) beagle dogs following one year of treatment. Dogs were prospectively randomized to one of five groups (N = 26): nondiabetic controls, Group I; dogs with DM on no antihypertensive drugs, Group II; dogs on a converting enzyme inhibitor, lisinopril (L), Group III; dogs on a calcium antagonist, TA3090 (diltiazem-like), Group IV; and dogs on a combination of each drug, in reduced doses, Group V. The current paper extends our previous studies by describing the morphologic changes that occurred within each group of dogs studied. More than 100 glomeruli from the renal cortex of each dog were evaluated for increases in mesangial volume fraction (Vv), glomerulosclerosis (GS) and ateriolar hyalinosis. The interstitium was also evaluated for associated changes. Increases in Vv were attenuated in all treated groups (0.28 +/- 0.04, DM alone versus 0.16 +/- 0.05 L; 0.21 +/- 0.07, TA-3090; 0.19 +/- 0.06 micron 2/micron 2, L+TA 3090; P < 0.05) compared to untreated DM. An attenuated increase in Vv also correlated with a blunted rise in proteinuria in Groups III (r = 0.79) and V (r = 0.81) but not Group IV (r = 0.29). Development of focal GS was blunted in all treated groups; however, global GS was fourfold greater in Group IV compared to untreated DM. The degree of interstitial fibrosis also correlated with the degree of global GS. These data support the concept that both a converting enzyme inhibitor and heart rate lowering calcium antagonist attenuate morphologic progression of diabetic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of different antihypertensive treatments on morphologic progression of diabetic nephropathy in uninephrectomized dogs. 793 34

The long-term effects of different antihypertensive regimens were studied in uninephrectomized beagles with alloxan-induced diabetes mellitus. Mean arterial pressure (MAP) was elevated (P < 0.05) in untreated diabetic dogs. Treatment of diabetic dogs with an angiotensin converting enzyme inhibitor (ACEI; lisinopril), a calcium antagonist (CA;TA-3090), or both lowered MAP. At one year, the RBF, GFR, and SNGFR were similarly elevated (P < 0.05) in all groups of diabetic dogs. The increase in SNGFR present in untreated diabetic dogs was primarily attributable to an increased (P < 0.05) glomerular capillary pressure (PGC). Treatment with lisinopril lowered the PGC to a mean value that was indistinguishable from that for nondiabetic dogs. In contrast, diabetic dogs treated with TA-3090 had an elevated PGC. While untreated diabetic dogs exhibited marked increases in glomerular volume (P < 0.05 vs. nondiabetic dogs), treatment with lisinopril and TA-3090, either alone or in combination, blunted the extent of glomerular hypertrophy observed in diabetic dogs (P < 0.05 vs. untreated diabetic dogs). Proteinuria was similarly reduced (P < 0.05 vs. untreated diabetic dogs) in dogs treated with lisinopril and TA-3090. Combination therapy of diabetic dogs produced a further significant (P < 0.05) decrement in proteinuria. We conclude that although treatment of diabetic dogs with either lisinopril or TA-3090 results in differential effects on PGC; each produces a similar decrement in proteinuria. Further, combination therapy has a greater effect on proteinuria than either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria. 839 Oct 95

One-third of diabetes mellitus patients develop diabetic nephropathy, and with underlying mechanisms unknown it is imperative that diabetic animal models resemble human disease. The present study investigated the susceptibility to develop diabetic nephropathy in four commonly used and commercially available mouse strains with type 1 diabetes to determine the suitability of each strain. Type 1 diabetes was induced in C57Bl/6, NMRI, BALB/c, and 129Sv mice by alloxan, and conscious glomerular filtration rate, proteinuria, and oxidative stress levels were measured in control and diabetic animals at baseline and after 5 and 10 wk. Histological alterations were analyzed using periodic acid-Schiff staining. Diabetic C57Bl/6 displayed increased glomerular filtration rate, i.e., hyperfiltration, whereas all other parameters remained unchanged. Diabetic NMRI developed the most pronounced hyperfiltration as well as increased oxidative stress and proteinuria but without glomerular damage. Diabetic BALB/c did not develop hyperfiltration but presented with pronounced proteinuria, increased oxidative stress, and glomerular damage. Diabetic 129Sv displayed proteinuria and increased oxidative stress without glomerular hyperfiltration or damage. However, all strains displayed intrastrain correlation between oxidative stress and proteinuria. In conclusion, diabetic C57Bl/6 and NMRI both developed glomerular hyperfiltration but neither presented with histological damage, although NMRI developed low-degree proteinuria. Thus these strains may be suitable when investigating the mechanism causing hyperfiltration. Neither BALB/c nor 129Sv developed hyperfiltration although both developed pronounced proteinuria. However, only BALB/c developed detectable histological damage. Thus BALB/c may be suitable when studying the roles of proteinuria and histological alterations for the progression of diabetic nephropathy.
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PMID:Differences in susceptibility to develop parameters of diabetic nephropathy in four mouse strains with type 1 diabetes. 2462 47

The present work deal with the effect of alloxan-induced diabetes on kidney oxidative stress and dysfunction of virgin and pregnant rat as well as the protection that may be afforded by high dosage GSSE (4g/kg) treatment. Diabetes affected negatively several kidney function parameters as creatinemia, uremia, uricemia and proteinuria without affecting kidney index. Diabetes also induced an oxidative stress characterized by increased lipid and protein oxidation, a drop in antioxidant enzyme defenses as catalase, superoxide-dismutase, glutathione-peroxidase, an alteration in transition metals as free iron, copper, selenium and associated enzymes and an increase in calpain and acetyl-cholinesterase activities. Tremendously, GSSE treatment protected efficiently against all the deleterious effects of diabetes-induced kidney dysfunction in both virgin and pregnant animals. High dosage GSSE is a safe and potent anti-oxidant that may be further tested in clinical trials for the long-term preservation of kidney function especially in multiple pregnancies.
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PMID:Protective effect of grape seed and skin extract against diabetes-induced oxidative stress and renal dysfunction in virgin and pregnant rat. 2745 14