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)

Heparan sulfate proteoglycans (HSPG) are negatively charged constituents of the renal extracellular matrix including the glomerular basement membrane (GBM) and mesangial matrix. Biochemical and functional studies of patients with type-1 insulin dependent diabetes mellitus (IDDM) suggest that alterations of HSPG may occur in diabetic nephropathy. We have utilized a specific cytochemical method and electron microscopy to quantitate the distribution of HSPG in the GBM of 10 normal people and in 16 IDDM patients with a spectrum of clinical and structural changes. Enzyme incubation studies of normal infant kidney demonstrated that heparitinase removed 94% of the stainable anionic sites in the lamina rara externa (LRE) and 77% of the sites in the lamina rara interna (LRI) of the GBM. In contrast, incubation in the enzyme chondroitinase ABC did not reduce the number of sites in the LRE but reduced the number of sites in the LRI by 26%. The HSPG anionic sites in normal subjects were distributed in the LRE as 20.9 +/- 1.3, and in the LRI as 13.1 +/- 2.2 per micron GBM length. Anionic sites were slightly reduced (19.6 +/- 1.3, P less than 0.04) in the LRE of IDDM patients with normal urinary albumin excretion rates (UAE), or microalbuminuria, and were reduced in both the LRE and LRI of IDDM patients with clinical proteinuria (13.1 +/- 2.3, P less than 0.001 and 8.9 +/- 2.1, P less than 0.001, respectively). The number of anionic sites in the LRE and LRI, respectively, correlated with UAE (r = +0.78, P less than 0.001, r = +0.58, P less than 0.02), with GBM thickness (LRE, r = +0.81, P less than 0.001; LRI, r = +0.67, P less than 0.01) and with the volume fraction of mesangium (LRE, r = +0.59, P less than 0.02; LRI, r = +0.58, P less than 0.03). These data confirm earlier biochemical findings of a reduction of HSPG in the GBM in advanced diabetic nephropathy but do not provide evidence for the loss of HSPG in the GBM as a mechanism for early microalbuminuria.
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PMID:Heparan sulfate proteoglycan in the glomerular basement membrane in type 1 diabetes mellitus. 151 88

The effect of streptozotocin-induced diabetes on the structure of heparan sulfate (HS) prepared from rat kidney glycosaminoglycans (GAG) was evaluated. GAG were isolated and purified from the kidneys of diabetic and age-matched control rats by standard procedures. HS was prepared from GAG by digestion with chondroitinase ABC and precipitation with cetylpyridinium chloride. The tissue dry weight of diabetic kidneys was greater than that of the controls. The amounts of protein and DNA per tissue dry weight were decreased in the diabetic group, while GAG and hydroxyproline remained unchanged. The above information indicates that the extracellular components are increased in diabetes. There was no significant difference in the amount of HS to tissue dry weight between the diabetic and control groups. When the molecular weight of the HS from both groups was compared by Sephacryl S-300 HR column chromatography, the HS peak for the diabetic kidney indicated a slightly higher molecular weight and the base of the peak was broader than that for the controls. A reduction in N-sulfate residues was observed in Sephadex G-50 profiles after nitrous acid degradation of the HS. The ratio of glucuronic acid to its epimer, iduronic acid, in diabetic kidney HS was slightly lower than that in the controls. This indicates that diabetes may influence the carbohydrate chain structure of the HS in the kidney. Quantitative and qualitative changes in the kidney HS may contribute to the symptoms associated with diabetic nephropathy.
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PMID:Effect of streptozotocin-induced diabetes on the structure of heparan sulfate from rat kidneys. 253 90

Using streptozotocin-induced diabetic Wistar and GK rats as models of type 1 and type 2 diabetes, respectively, we investigated the changes in serum and urinary hyaluronidase activity with the pathological progress. The serum hyaluronidase levels of streptozotocin-induced rats started to increase on the third day after injection and thereafter maintained approximately threefold higher levels compared with control rats; those of GK rats were already higher ( approximately twofold) from the beginning of the experiment. The increases of serum hyaluronidase activity in both diabetic rats were similar to those of blood glucose level, indicating that diabetes mellitus was accompanied by enhanced activity of circulating hyaluronidase from the early phase of its development. In zymography, every serum from diabetic and control rats gave two hyaluronidase isomers, a major 73-kDa band (Hyal-1 type) and a minor 132-kDa band, suggesting that the increases in serum hyaluronidase activity were not due to the appearance of novel isomers. The hyaluronidase activity in 24-h urine of streptozotocin-induced rats was 3-, 7-, and 11-fold higher at the 8th, 15th, and 18th week than that of control rats, respectively, and the urinary hyaluronidase activity of GK rats was not significantly different from controls. There was a good correlation between the urinary hyaluronidase activity and the albumin excretion. Thus the increase in urinary hyaluronidase activity may reflect enhanced glomerular permeability in streptozotocin-induced diabetic rats and may be a useful marker for diabetic nephropathy. Relative resistance to SDS-denaturation in zymography of rat serum and urinary hyaluronidases compared with human serum hyaluronidase are also shown.
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PMID:Enhanced activity of serum and urinary hyaluronidases in streptozotocin-induced diabetic Wistar and GK rats. 1455 Dec 18

We investigated changes in renal hyaluronidase activity in streptozotocin (STZ)-induced diabetic rats during the progression of diabetes. Prior to the study, we characterized rat renal hyaluronidase activity to find that its optimum pH is 3.5 and that it consists of two isomers of 73 and 63 kDa, as detected by zymography. Hyaluronidase activity was traced in one whole kidney and in the cortex and medulla of the other kidney up to the 18th week after STZ injection. Whole kidney hyaluronidase activity started to increase on day 3 and reached a maximum level 2.4 times that of the controls in the 3rd week. Cortical hyaluronidase showed a similar tendency to that of whole kidney hyaluronidase, while medullary hyaluronidase activity continued to increase until the 8th week, suggesting their different involvements in the progression of diabetic nephropathy. In zymography, the intensities of the two isomer bands increased with the progression of diabetes, but the intensity ratio did not change significantly and no new isomer band appeared. Renal HAase activity increased only in STZ-induced diabetic rats, but not in spontaneously diabetic Goto-Kakizaki rats still without remarkable renal disorder. Based on these findings, increased renal HAase activity may serve as a useful marker for diabetic nephropathy.
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PMID:Increased hyaluronidase activity in the kidney of streptozotocin-induced diabetic rats. 1476 77