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)

Tubular function was investigated in patients with diabetic ketoacidosis and those with poorly controlled type I diabetes. Urinary excretion of beta 2 microglobulin and that of certain enzymes: gamma glutamyltransferase, leucine aminopeptidase, and N-acetyl-beta-D-glucosaminidase activities were significantly raised during ketoacidosis in 11 patients compared with healthy controls. In 13 poorly controlled diabetics, tubular electrolyte transport was studied and a significant reduction in tubular phosphate and sodium reabsorption was found. Tubular dysfunction occurring during diabetic ketoacidosis and in poorly controlled diabetics may contribute to the development of diabetic nephropathy.
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PMID:Tubular dysfunction in type I diabetes mellitus. 393 37

To examine the relationships between the normal dietary intakes of protein and phosphate, blood pressure, and the progression of diabetic nephropathy, we prospectively studied 20 Type 1 diabetic subjects of mean age 43 +/- 10 years (SD) with early nephropathy (mean serum creatinine 115 +/- 43 mumol l-1) over 1 year. Three-monthly measurements of blood pressure, glycaemic control, and normal dietary intake (3-day weighed food records) and 6-monthly measurements of glomerular filtration rate (using a single injection of chromium 51-EDTA) were made. GFR changed at a median rate of -0.89 ml min-1 1.73 m-2 month-1 (range +0.85 to -2.55 ml min-1 1.73 m-2 month-1). Mean dietary protein intake (1.22 g kg-1; range 0.78 to 1.55 g kg-1) and phosphate intake (21.5 mg kg-1; range 14.1 to 30.4 mg kg-1) were not significantly related to the rate of change in GFR. Only mean systolic blood pressure was significantly related to change in GFR, and accounted for 45% of the variability in GFR decline in the 18 subjects who completed the study (r = 0.67; R2 = 0.449; F1,16 = 13.2; p < 0.005; 95% confidence interval for r: 0.336-0.867). A mean systolic blood pressure of 140 mmHg or below was associated with no significant decline in GFR over a median period of 13 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blood pressure, diet and the progression of nephropathy in patients with type 1 diabetes and hypertension. 820 Jan 98

Signs of glomerular, proximal and distal tubular dysfunction as well as metabolic control were studied in type 1 diabetes mellitus. To that end, the urinary excretion rates of albumin, sodium, phosphate and Tamm-Horsfall protein as well as HbA1c levels were measured in 20 patients with different degrees of diabetic nephropathy (positive Albustix for several years). Eight diabetic patients with short duration of diabetes and without any diabetic complications and 10 apparently healthy subjects were studied for comparison. The HbA1c levels in the three groups were 8.6 +/- 1.2, 5.9 +/- 2.2 and 4.1 +/- 0.4%, respectively (mean +/- SD). Duration of diabetes in the two diabetic groups were 27 +/- 7 and 3 +/- 1 years, respectively. The urinary protein levels were measured by enzyme-linked immunoassays. The fractional clearance of sodium (1.9 +/- 1.9%; p < 0.001) and phosphate (27 +/- 11%; p < 0.01) were increased in patients with diabetic nephropathy compared to diabetic patients without nephropathy (0.6 +/- 0.2 and 16 +/- 4%) and healthy control subjects (0.6 +/- 0.1 and 16 +/- 4%, respectively). Tamm-Horsfall protein excretion rate was decreased in both diabetic groups (15.0x/3.1 and 37.9x/1.9 micrograms/min, geometric mean x/tolerance factor, p < 0.001 and p < 0.05, respectively) compared to the healthy subjects (63.8x/1.3 micrograms/min). Furthermore, patients with diabetic nephropathy had a lower excretion rate of Tamm-Horsfall protein (15.0x/3.1 micrograms/min) compared to patients without signs of nephropathy (37.9x/1.9 micrograms/min, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tubular secretion of Tamm-Horsfall protein is decreased in type 1 (insulin-dependent) diabetic patients with diabetic nephropathy. 824 85

Recent clinical investigations have suggested that dietary protein intake may modulate the progression of diabetic nephropathy and influence glycaemic control in Type 2 (non-insulin-dependent) diabetes mellitus. Twelve normotensive Type 2 diabetic patients with microalbuminuria took part in a randomized cross-over trial of a 3-week high protein diet (2.0 g/kg.desirable weight per day) and a 3-week moderate protein diet (0.8 g/kg desirable weight per day) to test the simultaneous effect of protein intake modulation on glycaemic control and renal function. Both diets were isoenergetic and the moderate protein diet was supplemented with calcium and phosphate. Renal function and glycaemic control were evaluated at the beginning and at the end of each diet. The moderate protein diet reduced the urinary albumin excretion rate, glomerular filtration rate, creatinine clearance, and proteinuria without adversely affecting glycaemic control; fasting glycaemia and the ratio of fructosamine to proteins were significantly reduced. The high protein diet induced similar improvements in glycaemic control but small changes in renal function.
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PMID:Effect of protein intake on glycaemic control and renal function in type 2 (non-insulin-dependent) diabetes mellitus. 840 54

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

Activation of the polyol pathway under hyperglycemic conditions is proposed to contribute to the development of diabetic nephropathy. The mechanisms by which this activation may lead to functional and structural changes within the kidney are yet to be definitively established. We have examined in vitro the steps linking increased polyol pathway activity resulting from hyperglycemia to prostaglandin production. Following the demonstration of increased prostaglandin E (PGE) levels in glomeruli from diabetic rats (14.9 +/- 2.5 v 59.1 +/- 19.4 ng PGE/mg protein), a specific inhibitor of aldose reductase, HOE-843, was used in vitro to analyze the response to hyperglycemia of the steps preceding prostaglandin production. In explants of glomeruli from control animals, increasing the glucose concentration in vitro from 5.6 mmol/L to 25 mmol/L resulted in a significant increase in the flux of glucose through the pentose phosphate pathway ([PPP] 1.29 +/- 0.08 v 2.00 +/- 0.11 nmol/h), de novo diacylglycerol synthesis (2.2 +/- 0.1 v 3.1 +/- 0.2 micromol/mg protein), membrane protein kinase C (PKC) activity (18.7 +/- 0.5 v 24.3 +/- 0.75 pmol/microg protein), and in vitro phospholipase A2 (PLA2) activity (2.18 +/- 0.46 v 3.83 +/- 1.07 nmol arachidonic acid hydrolyzed/min/mg cytosolic protein). For all parameters measured, the increase resulting from the increased glucose concentration could be prevented by in vitro addition of HOE-843 for 24 hours before measurement. These findings provide evidence to suggest a mechanism linking increased polyol pathway activity and an increase in PLA2 activity to increased prostaglandin production, which is observed in diabetes of recent onset and may ultimately lead to changes associated with the development of diabetic nephropathy.
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PMID:Effect of inhibition of aldose reductase on glucose flux, diacylglycerol formation, protein kinase C, and phospholipase A2 activation. 900 67

Somatostatin modulates important physiologic functions of the kidney, including mesangial cell contraction, glomerular prostaglandin synthesis, and phosphate, water and sodium excretion. In diabetic nephropathy, somatostatin inhibits renal hypertrophy. High affinity somatostatin receptors are expressed in the kidney. Circulating somatostatin concentrations, however, are generally well below the affinity constants of known somatostatin receptors. Thus, we hypothesized that somatostatin is produced in the kidney and released locally to act in an autocrine/paracrine manner. Using reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, we found that fresh human renal cortex and cultured human mesangial cells express somatostatin mRNA. Restriction enzyme and Southern blot analysis confirmed that RT-PCR cDNA products were derived from somatostatin mRNA. Radioimmunoassay of mesangial cell culture supernatants demonstrated SS-immunoreactive peptide (87 +/- 30 pg/ml compared to 19 +/- 9 pg/ml in medium not exposed to cells; P < 0.05). In contrast, renal cells did not transcribe detectable levels of vasoactive intestinal peptide (VIP) or neuropeptide Y (NPY) mRNA, nor did they synthesize measurable peptide. Our results demonstrate that renal cells produce somatostatin and suggest that kidney-derived somatostatin may regulate renal function in an autocrine/paracrine manner. Characterization of this pathway may lead to novel methods to alter the course of diabetic nephropathy and other renal diseases.
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PMID:Somatostatin expression in human renal cortex and mesangial cells. 909 50

Advanced glycation endproducts (AGEs) are suggested to play an important role in diabetic nephropathy. They induce specific cellular responses such as the release of cytokines in different cell lines. The effect of AGEs on signal transduction pathways was investigated in the renal tubulus cell line LLC-PK1. Using a serine-phosphate-specific antibody AGE-induced cellular responses associated with phosphorylation/dephosphorylation events were demonstrated. In particular, the p42MAP kinase and its downstream target, the AP-1 complex, are shown to be activated by AGE-BSA but not by BSA. In contrast, only partial phosphorylation is observed for the p70S6-kinase. Thus, AGEs appear to induce specific signal transduction pathways.
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PMID:Advanced glycation endproducts stimulate the MAP-kinase pathway in tubulus cell line LLC-PK1. 923 87

Elevated urinary calcium and phosphate excretion have been observed in children with insulin-dependent diabetes mellitus (IDDM). This may be related to a defect in tubular reabsorption. It is well known that converting enzyme inhibition decreases microalbuminuria and may prevent or retard diabetic nephropathy. We investigated whether enalapril also improves the defect in calcium and phosphate reabsorption. We studied 16 children and young adults (age 12-21 years) with IDDM and persistent microalbuminuria before and during 12 weeks of enalapril treatment. Before treatment microalbuminuria, urinary calcium excretion, and fractional tubular phosphorus reabsorption (TPR) were 153+/-53 microg/min, 5.5+/-0.9 mg/kg per day, and 71.4+/-3.6%, respectively. At the end of the 12th week, microalbuminuria had decreased to 20.3+/-7.9 microg/min and calcium excretion to 3.3+/-0.4 mg/kg per day (P<0.01), while the TPR increased to 80.1+/-3.8% (NS). The renal threshold phosphate concentration increased from 1.8+/-0.15 to 2.92+/-0.23 mg/dl (P<0.01). The fasting serum glucose and hemoglobin Alc levels did not change significantly during the study. Systolic and diastolic blood pressures were 120.4+/-2.2 / 79.3+/-1.4 mm Hg and 110.5+/-1.8 / 71.3+/-0.9 mm Hg before and after 12 weeks, respectively. We conclude that enalapril treatment improves not only microalbuminuria but also abnormal calcium and phosphate excretion in microalbuminuric children with IDDM.
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PMID:Effect of enalapril on proteinuria, phosphaturia, and calciuria in insulin-dependent diabetes. 981 87

The hexosamine biosynthetic pathway has been hypothesized to be involved in the development of insulin resistance and diabetic vascular complications. In particular, it was demonstrated that hyperglycemia-induced production of transforming growth factor-beta (TGF-beta1), a prosclerotic cytokine causally involved in the development of diabetic nephropathy. Several lines of evidence indicate that TGF-beta1 induction is mediated by the hexosamine pathway. In cultured mesangial cells, high glucose levels induce TGF-beta1 production. This effect is eliminated by inhibition of glutamine: fructose-6-phosphate-amidotransferase (GFAT), the rate-limiting enzyme of this pathway. Furthermore, stable overexpression of GFAT increased levels of TGF-beta1 protein, mRNA, and promoter activity. Inasmuch as stimulation or inhibition of GFAT increased or decreased high glucose-stimulated activity of protein kinase C (PKC), respectively, the observed effects appear to be transduced by PKC. In similar experiments, involvement of the hexosamine pathway in hyperglycemia-induced production of cytokines (TGF-alpha and basic fibroblast growth factor [bFGF]) was demonstrated in vascular smooth muscle cells. These studies also revealed a rapid increase in GFAT activity by treatment with agents that elevated levels of cyclic adenosine 3',5' monophosphate (cAMP), thus indicating that GFAT activity is tightly regulated by cAMP-dependent phosphorylation. Using immunohistochemistry and in situ hybridization, high expression of GFAT was found in human adipocytes, skeletal muscle, vascular smooth muscle cells, and renal tubular epithelial cells. whereas glomerular cells remained essentially unstained. However, significant staining occurred in glomerular cells of patients with diabetic nephropathy. Current data indicate that the flux through the hexosamine pathway, regulated by GFAT, may be causally involved in the development of diabetic vascular disease, particularly diabetic nephropathy.
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PMID:Role of the hexosamine biosynthetic pathway in diabetic nephropathy. 1099 85


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