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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various biochemical parameters of renal tubular function were examined for a period of up to 12 weeks in rats rendered diabetic by an i.v. injection of streptozotocin. Except for a statistically significant decrease in the urinary excretion of gamma-glutamyl-transpeptidase to 64% of control values, the urinary excretion of beta-N-acetyl-D-glucosaminidase, beta-galactosidase, alanine aminopeptidase, and lactate dehydrogenase significantly increases in diabetic rats to between 154% and 712% of control values. This increased enzymuria is not correlated to the marked polyuria induced by diabetes (r between 0.14 and 0.35, not significant). Enzymuria is also accompanied by a 10-fold increase in the urinary excretion of the low molecular weight protein beta 2-microglobulin while the excretion of albumin is not significantly modified, indicating impairment of tubular reabsorption in diabetic animals. Clearance studies reveal that the clearance of both beta 2-microglobulin and infused egg-white lysozyme are also increased. Finally the histopathologic examination of paraffin sections of the kidney show hydropic degenerescence and pycnosis of the tubular cells. It is concluded that early-stage diabetes results in tubular impairment and that the streptozotocin-rat model appears well suited to the study of these early signs of renal dysfunction.
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PMID:Enzymuria and tubular proteinuria in diabetic rats: a 12-week follow-up study. 134 85

Enzymuria and specific proteinuria were examined over a period of 19 days in 4 groups of 5 rats: a control group, a nondiabetic polyuric group, a group of streptozotocin-induced diabetic rats treated with insulin as of the 10th day after the injection of the drug, and a similar group of untreated diabetic rats. Increased urinary excretion of beta-N-acetyl-D-glucosaminidase, lactate dehydrogenase, and alanine aminopeptidase was observed shortly after the induction of diabetes. It was partly or totally reversible following insulin treatment. Nondiabetic polyuria had a slight effect on the excretion of alanine aminopeptidase only. The urinary excretion of beta 2-microglobulin also rapidly increased after the onset of diabetes to a level approximately 50 times the control values. This effect was largely reversible with insulin treatment and was absent in the nondiabetic polyuric group. A small but significant 3-fold increase in albumin excretion was also noted but was not affected by insulin treatment. We conclude that streptozotocin-induced diabetes causes an early tubular dysfunction that is unrelated to polyuria and is reversible upon insulin treatment. This tubular dysfunction is best revealed by the urinary excretion of the low molecular weight protein beta 2-microglobulin. Our results suggest that it would be of interest to further examine the usefulness of sensitive markers of tubular dysfunction, especially low molecular weight proteinuria, in the detection of early stages of diabetic nephropathy.
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PMID:Reversibility of renal tubular dysfunction in streptozotocin-induced diabetes in the rat. 145 Oct 36

Amino-oligopeptidase (AOP, aminopeptidase N), a major glycoprotein hydrolase in intestinal and kidney brush border membranes, plays a crucial role in digesting peptide nutrients and salvaging filtered peptides. The molecular structure of rat intestinal and kidney AOP was compared for normal Wistar and congenitally diabetic BB Wistar (BBd) rats. Brush border membranes were isolated, solubilized with Triton X-100, and the AOP specifically immunoprecipitated with polyvalent rabbit antiserum and analyzed on 7% sodium dodecyl sulfate (SDS)-acrylamide electrophoresis. While the specific hydrolytic activity was maintained, BBd rats displayed an altered migration of AOP on SDS gels. Intestinal AOP migrated as a smaller species (130 kd) in the BBd than in the normal Wistar (135 to 140 kd). In some BBd rats, additional intestinal AOP species were observed (a 130- to 135-kd doublet or a 125-, 130-, or 135-kd triplet). Kidney AOP migrated as a broader band (125 to 140 kd) than intestine for all rat groups, probably due to carbohydrate chain heterogeneity, and was approximately 5 kd smaller in the BBd rat than in the normal Wistar. In contrast, no mass change was found in diabetes induced by streptozotocin (STZ). The altered intestinal AOP in the BBd rat was present when first inserted into the brush border membrane (6 hours after intraperitoneal [35S]methionine labeling), and hence was not due to nonenzymatic glycosylation (NEG). Abnormal intestinal and kidney AOP structure appeared in early diabetes, irrespective of high plasma glucose levels or ketoacidosis, and was reversed following evolution of the diabetes under prolonged (21 to 120 days) insulin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered intestinal and renal brush border amino-oligopeptidase structure in diabetes and metabolic acidosis: normal and biobreed (BB) rats. 153 46

The urinary excretion of kidney-specific marker proteins before and 120 hours after intravenous injection of either high- or low-osmolar contrast media (CM; diatrizoate, iopamidol 370) was monitored in patients after digital vascular imaging. Inclusion criteria for the randomized clinical study in a total of 40 patients (15 women, 25 men; mean age, 64.5 years) were at least 50 years of age or diabetes mellitus with normal creatinine concentration in serum. Compared with the control period, the elimination of tubular indicator enzymes alanine aminopeptidase, gamma-glutamyltranspeptidase, alkaline phosphatase, as well as of glomerular localized angiotensinase A was significantly higher in all patients after injection of the CM. The most significant differences were observed after 48 hours. In contrast, lysosomal N-acetyl-beta-D-glucosaminidase activity in urine specimens reacted less clearly and appears to be a less sensitive parameter in assessing CM nephrotoxicity. Elimination of brush border as well as of glomerular marker proteins was significantly lower after intravenous injection of low-osmolar CM iopamidol 370 (832 mOsm/kg) than after meglumine diatrizoate 76 (2100 mOsm/kg). In all 40 patients a significant decrease in creatinine clearance was observed; however, patients receiving diatrizoate had a significant decrease in creatinine clearance (period 0 versus 24 to 48 hours after CM), whereas patients after administration of iopamidol had not. No difference was found between creatinine clearance after 48 hours of CM injection within both groups of CM. Due to noninvasive parameters of kidney damage nonionic, low-osmolar CM are less nephrotoxic in potential risk patients, and should be preferred to conventional CM.
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PMID:Nephrotoxicity of high and low osmolar contrast media: case control studies following digital subtraction angiography in potential risk patients. 256 16

In a survey the present possibilities are outlined to get knowledge about diseases of inner organs with the help of enzyme determinations in the urine. Here it is remarkable that changes of the enzyme excretion appear not only in renal disease with acute renal failure, pyelonephritis, glomerulonephritis, renal infarction and nephroptosis but are also to be observed in primarily extrarenal diseases such as diabetes mellitus, hyperthyroidism, thesaurismoses, myocardial infarction, hypertension, acute pancreatitis, epidemic hepatitis, liver cirrhosis, obstructive jaundice and rheumatoid arthritis. The causes of the changes of enzyme excretions are various. Since enzymes of different origin and localisation behave themselves variably, the simultaneous determination of a brush border marker (e.g. alanine aminopeptidase), a lysosomal enzyme (e.g. beta-glucuronidase or N-acetyl glucosaminidase) and a low molecular enzyme (e.g. lysozyme) is of use for the recognition of renal alterations. By the control of activities of urinary enzymes it is possible to get without risk informations about pathobiochemical processes in the kidney which are not to be gained by means of other methods.
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PMID:[Urinary enzyme excretion in diseases of the internal organs]. 636 87

Serum ascorbic acid (AA) is reduced in diabetic patients. Aim of this study was 1) to verify whether such a decrease might be due to an altered urinary excretion of AA, and 2) whether this latter was modified in presence of early diabetic nephropathy with microalbuminuria (albumin excretion rate [AER] > 20 micrograms/min) in a group of 21 patients affected by insulin-dependent (type 1) diabetes mellitus (IDDM) as compared with 13 healthy controls matched for sex, age, dietary AA intake, and creatinine clearance per 1.73 m2 (CCl). Mean serum AA (+/- SD) was lower in diabetics (40.3 +/- 14 microM/l) than in controls (85.1 +/- 23.5 microM/l; p = 0.0001) and there was no difference between serum AA of patients with or without microalbuminuria. Urinary excretion of AA to creatinine x 100 (UAA/Cr) was higher in micro- (n = 6; 4.6 +/- 1.7) as compared to normoalbuminurics (n = 15; 1.6 +/- 0.9) or controls (1.5 +/- 1.2; p = 0.0001). For values exceeding renal threshold of tubular AA reabsorption (39 microM) the regression line of serum AA to UAA/Cr was significantly (p = 0.001) steeper in diabetics than in controls, suggesting an impaired tubular reabsorption of filtered AA in IDDM. The ratio of AA clearance to CCl was moreover related to AER (r = 0.48; p = 0.03) and to blood glucose (r = 0.51; p = 0.01), being unrelated to uric acid clearance, glycosuria and to urinary excretion of both alanine aminopeptidase and N-acetyl-beta-glucosaminidase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal excretion of ascorbic acid in insulin dependent diabetes mellitus. 796 Apr 90

In an in-depth examination to better define the renal effects of mild hypertension, we used urinary proteins to indicate damage to the glomerulus (albumin), tubular reabsorption capability (retinol-binding protein), and turnover of tubular tissue (alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase) in a group of 18 people with mild hypertension not associated with diabetes and a control group (n = 12). The participants' activity was controlled on a high normal salt diet for 3 days followed by a low salt diet for 4 days. Two distinct patterns of albumin excretion were evident in the hypertensive group: 22% had elevated, highly variable excretion patterns, and the rest had tightly grouped values below 16 mg/g creatinine, 16 micrograms/min, or 16 mg/L, with the lowest within-person biological variability given by albumin calculated as a ratio to creatinine. Albumin and NAG excretion primarily correlated with systolic blood pressure and the best correlations were given by ratios to creatinine. A marked decrease in salt excretion of 71% (to 50.8 mEq/day) resulted in significant (P < .0005) decreases in systolic (13.9 mm Hg), diastolic (6.4 mm Hg), and mean arterial pressures (8.9 mm Hg) only in the group with mild hypertension. However, albumin excretion did not decrease when dietary salt content was lowered. The group with hypertension also had higher urinary excretion of lysosomal N-acetyl-beta-D-glucosaminidase (P < .01), and whites in the group had a higher excretion of retinol-binding protein than did whites in the control group (P < .02). Retinol-binding protein values, however, were within the normal range, indicating that the elevated albumin values were the result of changes in selectivity of the glomerulus.
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PMID:An in-depth examination of the excretion of albumin and other sensitive markers of renal damage in mild hypertension. 855 30

The effect of lead on five renal-effect parameters was studied in 151 children (i.e., 3-6-y-olds) who resided at different distances from a lead smelter in Baia Mare, Romania. A relationship was found between concentration of lead in blood (mean +/- standard deviation: 342 +/- 224 microgram/l) and the activity of N-acetyl-beta-D-glucosaminidase in urine, as demonstrated by a 14% increase of N-acetyl-beta-D-glucosaminidase per 100 micrograms/l blood lead that was indicative of renal tubular damage. No relationship was found between blood lead level and the renal-effect parameters albumin, alpha-1-microglobulin, retinol binding protein, or alanine aminopeptidase in urine. Cadmium in blood was not elevated. It is well known that N-acetyl-beta-D-glucosaminidase is a sensitive parameter for renal effects, resulting from lead exposure in adults and from diabetes and nephrotoxic medicines in children. This study is the first to demonstrate an effect of environmental lead exposure on renal integrity in children.
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PMID:Environmental lead and renal effects in children. 901 27

In patients suffering from insulin-dependent diabetes mellitus (IDDM) with or without preclinical and clinical signs of diabetic nephropathy, the degree of epithelial cell lesions in the renal tubules was assessed from the urinary activities of enzymes at various sites, such as lysosomal (N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (beta-GA)), brush edge membranous (alanine aminopeptidase (AAP), and cytosolic (alpha-glucosidase (alpha-GL)). Patients from Groups 1 and 2 had no preclinical and clinical signs of nephropathy. In Group 1 patients, the magnitude of enzymuria was not different from that in normalcy. However, Group 2 patients exhibited significant increases in urinary NAG and beta-GA activities as compared to Group 1 patients and healthy individuals. In Group 3 patients with microproteinuria from 0.05 to 0.5 mg protein per ml urine, displayed a further enhancement of NAG and beta-GA activities as compared to Group 2 patients and significantly higher activity than did Groups 1 and 2 patients and healthy individuals. In Group 4 patients with macroproteinuria of > 0.5 mg/ml), greater increases in the activities of NAG, beta-GA, and AAP were not found, however, there was a significant increase in alpha-G1 activity. The findings suggest the varying degrees of epithelial cell damage in the renal tubules in patients of different groups and the possibility of early detection of lesion in the proximal portion of nephronic tubules in IDDM patients as assessed from urinary enzyme levels.
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PMID:[Urinary enzymes in insulin-dependent diabetes mellitus]. 899 62

It is well established that the detection of microalbuminuria in a patient with diabetes mellitus indicates the presence of glomerular involvement in early renal damage. Recent studies have demonstrated that there is also a tubular component to renal complications of diabetes, as shown by the detection of renal tubular proteins and enzymes in the urine. In fact, tubular involvement may precede glomerular involvement, as several of these tubular proteins and enzymes are detectable even before the appearance of microalbuminuria. This review looks at the studies reported so far on serum and urinary markers of diabetic nephropathy, both glomerular and tubular, and their roles in the early detection of renal damage. The advantages and disadvantages of some of these markers are also discussed. The markers reviewed include (1) glomerular--transferrin, fibronectin, and other components of glomerular extracellular matrix, and (2) tubular--low molecular weight proteins (beta 2 microglobulin, retinol binding protein, alpha 1 microglobulin, urine protein 1), other proteins such as Tamm-Horsfall protein, beta 2 glycoprotein-1, urinary enzymes (N-acetyl-beta-D-glucosaminidase, cholinesterase, gamma glutamyltranspeptidase, alanine aminopeptidase), and tubular brush-border antigen.
J Diabetes Complications
PMID:Markers of diabetic nephropathy. 944 15


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