UMLS:C0011881 - FACTA Search

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Query: UMLS:C0011881 (diabetic nephropathy)
10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The genetically determined acetylator phenotype in diabetic children with and without increased urinary albumin excretion was investigated. Acetylator phenotype was determined according to Evans, and 24-hour albumin excretion rate (AER) was measured by immunoturbidometry in 86 children and adolescents with type 1 (insulin-dependent) diabetes mellitus and in 100 age-matched healthy controls. In diabetics, the fast acetylator phenotype was found in 36 (41.9%) patients and the slow one in 50 (58.1%); the control group had 52 (52%) fast and 48 (48%) slow acetylators. There were no significant differences in acetylator phenotypes between diabetic patients and control subjects (chi 2 = 1.0, NS). Among patients with normal albumin excretion (n = 70, mean age: 12.9 +/- 3.5 years, mean diabetes duration: 5.3 +/- 3.8 years, AER < 20 micrograms/min), 35 (50%) fast acetylators and 35 (50%) slow acetylators were found. In patients with elevated albumin excretion (n = 16, mean age: 14.0 +/- 3.2 years, mean diabetes duration: 4.9 +/- 3.0 years, AER > 20 micrograms/min), 1 (6.3%) patient was a fast acetylator and 15 (93.7%) were slow acetylators. A significant difference has been found between the two groups in the rate of fast/slow acetylators (chi 2 = 8.79, p < 0.01). The strong correlation between the slow acetylator phenotype and microalbuminuria in diabetics suggests that: (a) genetic factors may play a role in the development of diabetic nephropathy; (b) the acetylator status could be a useful tool to detect patients 'at risk' of nephropathy.
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PMID:Association of microalbuminuria with slow acetylator phenotype in type 1 diabetes mellitus. 147 91

The effect of a 30% restricted diet on the development of diabetes and diabetic nephropathy was examined using the Otsuka Long Evans Tokushima Fatty (OLETF) rat which develops non-insulin-dependent diabetes mellitus (NIDDM) spontaneously after 25-30 weeks of age. The first experimental group that received 30% restricted feeding from six to 80 weeks old, showed complete suppression of spontaneous diabetes up to 40 weeks of age and showed milder histopathological change of pancreatic islets, that those of the control group. The second group which received 30% restricted feeding during 30-80 weeks, showed a gradual decrease in clinical diabetes with age, even though they had already developed diabetes at 25 weeks. In both groups, levels of urinary protein content appeared to decrease, compared with that in control rats, although a gradual increase of urinary protein was observed with age. Histopathologically, glomerular damages were slight to mild in both groups. However, no improvement in nephrotic complication was observed for the group which received a 30% restricted feeding after 70 weeks of age. These results clearly show that the balanced-control diet, given at a 30% restricted feeding level and at an early phase, is effective in the prevention or improvement of NIDDM and nephrotic complications. Diet therapy after 70 weeks of age, however, had little or no effect.
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PMID:Relationships between diet control and the development of spontaneous type II diabetes and diabetic nephropathy in OLETF rats. 892 35

This study evaluated the effects of treatment with an inhibitor of advanced glycation endproducts, aminoguanidine, on the development of albuminuria, mesangial expansion and glomerular basement membrane (GBM) thickening in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which we found to be an excellent model of non insulin-dependent diabetes mellitus (NIDDM), for its very close similarity to human NIDDM. OLETF rats were randomized into a non-treatment diabetic group (D-group, n = 5) and an aminoguanidine-treated group (AG-group, n = 5). The AG-group was given 100 mg/dl aminoguanidine HCl in free drinking water. Treatment was started at 16 weeks of age. We measured body weight, plasma glucose, total cholesterol, triglycerides and the urinary albumin excretion (UAE) rate before and after treatment at regular intervals. At 56 weeks of age, we measured serum advanced glycation endproducts (AGE), mesangial expansion and glomerular basement membrane. There were no significant differences in pre-treatment body weight, plasma glucose and UAE between the D-group and the AG-group. Likewise, after treatment there were no significant differences in body weight, plasma glucose, total cholesterol, triglycerides and immunoreactive insulin. Significant differences were, however, noted in serum AGE (63.2 +/- 3.5 and 51.8 +/- 3.0 U AGE/ml, P < 0.05), UAE (203.6 +/- 37.7 and 89.8 +/- 18.6 mg/day, P < 0.05), fractional mesangial volume (21.3 +/- 1.7 and 16.7 +/- 0.8%, P < 0.05) and GBM thickness (453 +/- 17 and 366 +/- 50 nm, P < 0.05) between the D-group and the AG-group. Our results suggest that aminoguanidine inhibits the AGE formation and the development of diabetic nephropathy in OLETF rats.
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PMID:Effects of aminoguanidine on serum advanced glycation endproducts, urinary albilmin excretion, mesangial expansion, and glomerular basement membrane thickening in Otsuka Long-Evans Tokushima fatty rats. 906 63

Increases in extracellular matrix (ECM) and changes in its components have been documented in the glomeruli of diabetic nephropathy. Advanced glycation end products formed by glycoxidation have been shown to induce the synthesis of ECM components and transforming growth factor beta (TGF-beta), suggesting that advanced glycation end products may be involved in the etiology of imbalance of ECM components in diabetic glomerulosclerosis. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an inbred strain that spontaneously develops non-insulin-dependent diabetes mellitus which progresses to diabetic glomerulosclerosis. Nepsilon-(carboxymethyl)lysine (CML) is known to be formed by glycoxidation. To clarify the involvement of glycoxidation in diabetic nephropathy, we examined the localization of CML, ECM components, and TGF-beta1 in the glomeruli of OLETF rats. The amounts of alpha3(IV) collagen, type VI collagen, and fibronectin were significantly increased in the glomeruli of OLETF rats, whereas the heparan sulfate proteoglycan levels were decreased. After 6 months of age, CML levels were significantly increased in the mesangial area of the glomeruli in these animals. The overexpression of TGF-beta1 preceded the increase in glomerular ECM components. The present study demonstrated that the accumulation of CML precedes the changes of glomerular ECM components in the glomeruli during the course of diabetic nephropathy, suggesting that glycoxidation may be one of the major causes of diabetic glomerulosclerosis.
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PMID:Accumulation of Nsigma-(carboxy-methyl)lysine and changes in glomerular extracellular matrix components in Otsuka Long-Evans Tokushima fatty rat: a model of spontaneous NIDDM. 968 63

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new genetic model of non-insulin-dependent diabetes mellitus (NIDDM). We investigated whether treatment with an angiotensin II (ANGII) subtype-1 receptor antagonist delays the onset of NIDDM and attenuates diabetic nephropathy in the OLETF rat. OLETF rats fed a regular chow were treated with ANGII subtype-1 receptor antagonists (E4177 or TA606) for 22 weeks. Hemodynamic changes, glucose metabolism, and the effects on diabetic nephropathy were examined. Systolic blood pressure increased in OLETF rats in an age-dependent manner. OLETF rats exhibited increases in plasma concentrations of glucose and insulin and developed glucosuria at the age of 28 weeks. The changes in glucose metabolism were associated with proteinuria and an increase in urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Morphologic investigation revealed nodular lesions in glomeruli in the OLETF rats. The ANGII receptor antagonist treatment abolished the blood pressure elevation. However, the treatment did not affect plasma glucose and insulin levels and did not significantly reduce glucosuria. Nodular lesions in glomeruli were not improved by the treatment. However, the receptor antagonists significantly reduced proteinuria and urinary NAG excretion. Multivariate analyses revealed that proteinuria was determined by systolic blood pressure, lipid metabolism, and glucose levels in plasma. ANGII subtype-1 antagonism does not improve glucose metabolism in the OLETF rat model of NIDDM, which has abnormalities in the glucose-uptake system. Blood pressure elevation and part of the proteinuria associated with NIDDM depends on the renin-angiotensin system rather than glucose metabolisms per se.
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PMID:Angiotensin II subtype-1 receptor antagonists improve hemodynamic and renal changes without affecting glucose metabolisms in genetic rat model of non-insulin-dependent diabetes mellitus. 1007 80

Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P < 0.01) but failed to increase in DI-DM. Urinary albumin excretion more than doubled in LE-DM but rose by only 34% in DI-DM rats (P < 0.05). Kidney hypertrophy was also less intense in DI-DM than in LE-DM (P < 0.001). These results suggest that VP plays a critical role in diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.
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PMID:Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats. 1046 19

In an investigation of the involvement of prostanoids in the pathogenesis of nephropathy in type 2 diabetes, we repeatedly measured the urinary excretion of prostanoids in both diabetic and healthy rats as the rats aged. Seven rats of the Otsuka Long-Evans Tokushima Fatty strain were used as rats with a model of type 2 diabetes and seven rats of the Long-Evans Tokushima Otsuka strain were used as rats without diabetes. Thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1alpha, the amounts of which reflect renal production of TXA2 and PGI2, respectively, and PGE2 in urine collected in metabolic cages were assayed when rats were 14, 30, 46, and 54 weeks old. Plasma glucose and urinary protein excretion also were measured periodically. The mean plasma glucose concentration of the diabetic rats was higher than that of the healthy rats throughout the study. At 30 weeks and later, urinary protein excretion by the diabetic rats was greater than that of the healthy rats, and it increased with age. Urinary excretion of TXB2 by the diabetic rats was higher than that of the healthy rats at 14 weeks (52.4+/-23.5 vs. 27.0+/-2.6 ng/day; mean +/- SD, P = .015) and the difference continued to the end of the experiment. Urinary excretion of 6-keto-PGF1alpha by the diabetic rats was high at 14 weeks (52.3+/-12.8 vs. 26.9+/-4.6 ng/day; mean +/- SD, P<.001) but decreased with age and was the same as that of the healthy rats at 54 weeks. The urinary excretion of PGE2 by the two groups of rats was not significantly different. These results suggest that altered renal production of TXA2 and PGI2 is involved in the pathogenesis of diabetic nephropathy in rats with type 2 diabetes.
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PMID:Renal production of thromboxane and prostaglandins in a rat model of type 2 diabetes. 1067 Aug 25

Diabetic nephropathy is a common cause of end-stage renal disease. The administration of an oral adsorbent, AST-120, prevents the progression of chronic renal failure in uremic rats and undialyzed uremic patients. This study was designed to determine if AST-120 slows the progression of diabetic nephropathy using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetic mellitus. At 21 weeks of age the OLETF rats were divided into 2 groups: AST-120-administered OLETF rats (n = 7), and control OLETF rats (n = 7). LETO rats, which are genetically similar to the OLETF rats but not diabetic, were also included. After the oral administration of AST-120 for 65 weeks, renal function and pathological changes were investigated in the 3 groups. The administration of AST-120 to the OLETF rats attenuated the progression of glomerular sclerosis, interstitial fibrosis, tubular injury as well as renal dysfunction, and reduced the serum and urinary levels of indoxyl sulfate. Furthermore, AST-120 administration reduced the interstitial expression of transforming growth factor (TGF)-beta(1) and tissue inhibitor of metalloproteinase (TIMP)-1, as well as interstitial infiltration of macrophages. The TGF-beta(1)-stained interstitial area showed positive correlations with the interstitial fibrosis area, the number of TIMP-1-positive cells, and the number of macrophages, and showed a negative correlation with creatinine clearance. In conclusion, AST-120 reduced the interstitial expression of TGF-beta(1) and TIMP-1, and the interstitial infiltration of macrophages, and ameliorates the progression of diabetic nephropathy in OLETF rats.
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PMID:Oral adsorbent AST-120 ameliorates interstitial fibrosis and transforming growth factor-beta(1) expression in spontaneously diabetic (OLETF) rats. 1087 8

In diabetes mellitus (DM), the urine flow rate is increased, and the fluid turnover in the body is accelerated because of the glucose-induced osmotic diuresis. On the other hand, plasma vasopressin (VP) is elevated in both type 1 and type 2 DM. This elevation seems to be due to a resetting of the osmostat. A high VP level is beneficial in the short term because it limits to some extent the amount of water required for the excretion of a markedly enhanced load of osmoles (mainly glucose). However, in the long run, it may have adverse effects by favoring the development of diabetic nephropathy. VP has been shown in normal rats to induce kidney hypertrophy, glomerular hyperfiltration, and an increase in urinary albumin excretion (features also occurring in association in the period preceding diabetic nephropathy). Moreover, VP has been shown to participate in the progression of renal failure in rats with five-sixths reduction in renal mass. In recent studies, we have shown (1) that creatinine clearance, albuminuria and renal mass increased much less during experimental DM in Brattleboro rats unable to secrete VP than in their VP-replete Long-Evans controls, and (2) that albuminuria was prevented during experimental DM in Wistar rats when a VP nonpeptidic, highly selective V2 receptor antagonist was administered chronically for 9 weeks. Taken together, these results strongly suggest that VP plays a crucial role in the onset and aggravation of the renal complications of DM. The mechanisms by which VP exerts these adverse V2-dependent effects are not yet elucidated. They are most likely indirect and may involve several intermediate steps comprising VP-induced changes in the composition of the tubular fluid in the loop of Henle (due to solute recycling in the renal medulla associated with improved concentrating activity of the kidney), inhibition of the tubuloglomerular feedback control of glomerular function, and alterations in glomerular hemodynamics by the intrarenal renin-angiotensin system.
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PMID:Vasopressin and diabetes mellitus. 1117 21

To investigate the long-term effects of normal pancreatic islet transplantation on progression of obese type 2 diabetes mellitus (DM), 1500 normal islets (per rat) from Wistar King A rats at 8 weeks of age were transplanted into the liver through the portal vein of Otsuka Long Evans Tokushima Fatty (OLETF) rats, an animal model of obese type 2 DM, at 12 weeks of age. Body weight in the transplanted OLETF (IT) rats 8 and 28 weeks after islet transplantation did not differ from that in the corresponding sham-operated (SO) rats, but was greater than that in lean littermates (LETO rats; P < 0.05 for each group). In the early phase, 8 weeks after transplantation, rats in both IT and SO groups were normoglycemic, but hyperinsulinemic (P < 0.05 for each compared with LETO rats), probably resulting from increased body weight. In the late phase, 28 weeks after transplantation, hyperglycemia in the IT group was greatly attenuated compared with the SO group (P < 0.05), but hyperinsulinemia remained in both the IT and the SO groups compared with that in the LETO group (P < 0.05 for each). Immunohistochemical studies demonstrated that hypertrophic and fibrotic changes in pancreatic islets, together with mesangial proliferation of the glomerular matrix, an indicator for diabetic nephropathy, were attenuated predominantly in the IT group at the late phase after transplantation compared with those in the corresponding phase of the SO group. Islet transplantation into the liver of OLETF rats thus prevented further progression of obese type 2 DM. A possible mechanism is that islet transplantation may prevent development of hyperglycemia by improving abnormal hepatic glucose metabolism and consequently insulin resistance, which may lead to blockade of a vicious cycle between advancing damage to pancreatic islet cells and increased demand for insulin secretion, thus sparing original pancreatic cells from exhaustion induced by increased demand for insulin secretion.
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PMID:Transplantation of normal islets into the portal vein of Otsuka Long Evans Tokushima Fatty rats prevents diabetic progression. 1144 4

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