Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated urinary N-acetyl-beta-glucosaminidase (NAG) excretion in overnight and in second morning urine in 50 young diabetic patients, aged 7.4-25 years with a disease duration from 2-19.6 years. In all patients we evaluated urinary NAG and creatinine excretion, in both overnight and second morning urine, glycosuria, fasting blood glucose and HbA1c levels, insulin requirement, blood pressure, and the presence of microangiopathic complications. Urinary NAG excretion was also evaluated in 69 age- and sex-matched controls. NAG was determined using 3-cresolsulfonphtaleinyl-beta-N-acetylglucosaminide as substrate (Boehringer Mannheim, Germany). In the diabetic patients NAG/Cre ratios were significantly higher than in controls both in overnight and second morning urine (P < 0.0005, respectively). We observed significantly higher NAG/Cre ratio levels in the second morning than in overnight urine, both in controls and in diabetics (P < 0.0005, respectively). Elevated (above 2 S.D. of the mean) NAG/Cre ratios were found in 17/50 patients (34%) in overnight urine and in 29/50 (58%) in second morning urine. No correlation was observed between NAG/Cre ratio levels and age, duration of disease, pubertal stage, body mass index, fasting blood glucose, glycosuria, insulin requirement and blood pressure. The patients with one or more complications did show NAG/Cre ratio levels significantly higher than those without complications (P < 0.005) in second morning urine, but not in overnight urine. Our study has demonstrated an increased rate of urinary NAG excretion in young IDDM patients, in particular in those with microangiopathic complications.
Diabetes Res Clin Pract 1995 Aug
PMID:Increased urinary N-acetyl-beta-glucosaminidase (NAG) excretion in young insulin-dependent diabetic patients. 859 5

This study was undertaken to determine whether there are age-related changes in the specific activities of several glycosidases in fresh retinal pigment epithelial cells (RPE) isolated from the posterior pole of human donor eyes. One hundred and twenty-one pairs of eyes from human donors, between the ages of 43 and 95 years, were obtained from the National Disease Research Interchange (NDRI, Philadelphia, PA) and the Cleveland Ohio Eye Bank within 18 to 24 h of death. None had histories of diabetes, hepatitis, HIV infection, intraocular surgery, or documented age-related macular degeneration, although several older donors with evidence of drusen were included in the study. RPE cells were isolated from the posterior third of the retina using the conventional rush method and homogenized with a glass, Broeck tissue grinder. All post-nuclear supernatants were analyzed for glycosidase activity; a smaller number of nuclear pellets were assayed to verify that the majority of the enzyme activity was associated with the post-nuclear sypernatants. Glycosidase activity was quantitated fluorometrically by measuring the enzymatic release of umbelliferone from synthetic substrate preparations, specific for each enzyme. Total protein was determined by a micro BCA protein assay. Regression analysis revealed statistically significant age-related decreases for the specific activities of alpha-mannosidase (p = 0.0001), beta-galactosidase (p = 0.0001), N-acetyl-beta-glucosaminidase (p = 0.0001), and N-acetyl beta galactosaminidase (p = 0.0001) in fresh human donor RPE cells taken from the region of the posterior third of the retina that included the macula. Mannose and N-acetyl-glucosamine are major carbohydrate monomers of the oligosaccaride chains of human rhodopsin, and a relatively high percentage of the oligosaccharide chains are galactosylated. Defects in their degradation may lead to the accumulation of undigested residual material in the RPE.
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PMID:Age-related changes of glycosidases in human retinal pigment epithelium. 867 Jul 43

To investigate the extra susceptibility of diabetics to some nephrotoxic agents, adult normal and diabetic Chinese hamsters (6-7 animals in each group) were injected subcutaneously with different doses of cadmium-metallothionein (Cd-MT) equivalent to 0.0, 0.1 or 0.25 mg Cd/kg body weight and the first 24 hr urinary outputs were collected. Several days prior to exposure to the Cd-MT the diabetic hamsters were hyperglycaemic, and plasma insulin levels and body weights were elevated in some of the diabetics. The higher dose of Cd-MT caused significant spillage of N-acetyl-beta-glucosaminidase (U-NAG) activity and protein into the urine of both normal and diabetic animals. The higher dose of Cd-MT was more toxic to the diabetic kidneys because U-NAG levels were higher in the diabetics (2.5-fold higher than normal). U-Cd levels were proportional to the injected Cd-MT dose. U-Zn levels were not consistently affected by the injected Cd-MT although it had contained small amounts of Zn. Therefore, genetic diabetes in the Chinese hamster appears to increase susceptibility to acute cadmium-MT nephrotoxicity. The mechanisms underlying this need to be further investigated.
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PMID:Cadmium-metallothionein nephrotoxicity is increased in genetically diabetic as compared with normal Chinese hamsters. 888 66

Twenty-four-hour urine specimens from 21 juvenile insulin-dependent diabetics and 10 healthy controls were compared with respect to biotinidase activity and alanine content. Urinary biotinidase activity was analysed by a newly developed high-performance liquid chromatography (HPLC) method. It was found that the excretion of biotinidase in urine was elevated in diabetics (7.02 mU/d; p < 0.005) as compared with controls (not detectable). Alanine excretion was also found to increase (p < 0.01) in diabetics. Biotinidase excretion in diabetics was correlated with alanine excretion (rS = 0.667; p < 0.01), but not with protein, albumin or N-acetyl-beta-glucosaminidase excretion. The simultaneous elevation of urinary biotinidase and alanine excretion in juvenile diabetics suggests that changes in kidney metabolism arise in the early stages of diabetes.
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PMID:Urinary biotinidase and alanine excretion in patients with insulin-dependent diabetes mellitus. 915 61

Serum N-acetyl-beta-glucosaminidase activity was evaluated in 40 Type 1 and 40 Type 2 diabetic patients and compared with parameters of diabetes control and oxidative stress. Significantly increased mean serum N-acetyl-beta-glucosaminidase activity was found in both groups of diabetic patients as compared with the corresponding group of healthy persons (p < 0.01). Oxidative stress measured by plasma malondialdehyde concentration was significantly higher in Type 2 than in Type 1 diabetic patients (p < 0.01) but in comparison with control subjects it was higher only in Type 2 diabetes. Plasma malondialdehyde concentration positively correlated with body mass index (r=0.77, p<0.001) and with serum N-acetyl-beta-glucosaminidase activities (r=0.57, p <0.001). Treatment of 10 Type 2 diabetic patients with antioxidant alpha-tocopherol caused a significant decrease in malondialdehyde concentration (p < 0.001) which was accompanied by a decrease of N-acetyl-beta-glucosaminidase activity (p < 0.01). We conclude that serum N-acetyl-beta-glucosaminidase activity may be influenced by oxidative stress which is more pronounced in Type 2 than in Type 1 diabetic patients.
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PMID:Relationship of serum N-acetyl-beta-glucosaminidase activity to oxidative stress in diabetes mellitus. 1034 Apr 45

Glycosaminoglycan sulodexide may influence morphology and functional properties of the basement membranes in microvessels. The aim of this study was to evaluate the effect of sulodexide administration on albuminuria and on different biochemical variables indicating endothelial dysfunction, oxidative stress and fibrinolysis in diabetic patients. Twenty diabetic patients of both types with micro- or macroalbuminuria were selected for sulodexide treatment. Daily dose of 600 U (60 mg) was injected intramuscularly five days a week. Fifteen doses were applied during 3 weeks. The patients were examined before and after treatment as well as 6 months later. No changes of diabetes control were observed during the study and after 6 months of wash-out period. Significant decrease of albuminuria (p < 0.001) was observed during the sulodexide administration with the following increase to pretreated values during the wash-out period. A decrease of serum N-acetyl-beta-glucosaminidase (NAG) activity (p < 0.03) at the end of treatment as compared to pretreated values was found in the whole group of diabetic patients. Slight reduction of oxidative stress expressed by malondialdehyde and superoxide dismutase was apparent after treatment but no simultaneous change in fibrinolysis was observed. Sulodexide may have some protective effects influencing functional properties of the basement membrane as manifested by lowered albuminuria. In addition, it may slightly decrease oxidative stress in diabetic patients and it could stabilize endothelial cells.
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PMID:The effect of glycosaminoglycan sulodexide on oxidative stress and fibrinolysis in diabetes mellitus. 1053 89

The aim of this study was to compare biochemical markers of endothelial activation with microcirculation measured by laser-Doppler flowmetry in Type 1 diabetic patients with or without microangiopathy. A total of 44 Type 1 diabetic patients were subdivided into those with (n=24) and without (n=20) microangiopathy according to ophthalmological findings and the presence or absence of microalbuminuria. The control group consisted of 25 healthy people of comparable age, sex, and body mass index. Postocclusive reactive hyperemia (PORH) and thermal hyperemia (TH, at 44 degrees C) were measured at the forearm. Serum N-acetyl-beta-glucosaminidase (NAG) activity, serum E-selectin, and ICAM-1 concentrations were used as biochemical markers of endothelial dysfunction. A significantly lower velocity of perfusion increase during postocclusive hyperemia (PORH(max) x t(1)(-1)) and during thermal hyperemia (TH(max) x t(2)(-1)) (P<.01) were accompanied by higher serum NAG activity (20.9+/-4.6 vs. 16.3+/-2.5 U l(-1), P<.01) in diabetic patients with microangiopathy as compared to healthy persons. An inverse relationship was found between PORH(max) x t(1)(-1) and NAG (r=-.33) results in diabetic patients. In addition, higher mean values of serum NAG activity, E-selectin, and ICAM-1 concentrations were associated with significantly lower values of microcirculation parameters (PORH(max) x t(2)(-1) and TH(max) x t(2)(-1)) in six patients without microangiopathy who had at least one of the above biochemical markers higher than mean+2 S.D. range. We suggest that serum NAG activity, E-selectin, and ICAM-1 concentrations may be used together with laser-Doppler flowmetry in Type 1 diabetic patients as early indicators of vascular changes in very early stage of diabetic microangiopathy.
J Diabetes Complications
PMID:Comparison of laser-Doppler flowmetry with biochemical indicators of endothelial dysfunction related to early microangiopathy in Type 1 diabetic patients. 1152 96

The role of dietary fibers in diabetes has been studied by several workers. Long term dietary treatment with increased amounts of fiber-rich low-glycaemic index natural foods improves blood glucose and reduces the number of hypoglycemic events in type I diabetic patients. On the other hand Rohrbach and Martin and Cohen and Surma described changes in the general and biochemical structure of renal tissues such as the glomerular basement membranes. One of these changes was the reduction and undersulfation of the glycoconjugate and glycosaminoglycan heparan sulfate, which plays an important role in renal structure and function. The purpose of the present study was to determine specific effects of two types of dietary fiber on the composition of kidney glycoconjugates in an animal model of diabetes type I. Streptozotocin-treated diabetic rats were fed either a control diet or diets containing 10% wheat bran (insoluble dietary fiber) or 5% guar gum (soluble dietary fiber). Effects of these fibers on glycaemic control and nephropathy were assessed using previously described methodologies. The effect of dietary fiber in the glycoconjugate composition of kidneys of control and diabetic animals was studied by estimating their total hexose content, sulfated glycosaminoglycans, hexosamines and uronic acids. The activities of enzymes that participate in the synthesis of saccharides and glycoconjugates (L-glutamine-fructose-6-phosphate aminotransferase) and their degradation (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were also evaluated. Results indicated that both soluble and insoluble dietary fibers ameliorated a significant increase in the activity of GFAT. Heparan sulfate was also isolated and quantified. Results indicated that the renal content of heparan sulfate decreased in diabetic animals and that this decrement was ameliorated by the ingestion of both soluble and insoluble fiber in the diet.
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PMID:Dietary fibres ameliorate decreased synthesis of heparan sulphate in streptozotocin induced diabetic rats. 1277 Jun 44

Statins and fibrates influence endothelial activity and consequently atherogenesis but the mechanisms are not well understood. Twenty Type 2 diabetic patients with dyslipidemia were treated 3 months with simvastatin (20 mg daily) and then 3 months with fenofibrate (200 mg daily) with 2 months of wash-out between the two treatments. Laboratory parameters of oxidative stress, fibrinolysis and endothelial function were evaluated before and at the end of each treatment period. The significant decrease in serum total and LDL-cholesterol concentrations (P<0.0001) caused by simvastatin was associated with an increase in serum N-acetyl-beta-glucosaminidase activity (P<0.001), ascorbic acid (P<0.001), plasminogen activator inhibitor (PAI-1) (P<0.01), vonWillebrand factor (P<0.05), E-selectin (P<0.01) and vascular endothelial growth factor (P<0.05) concentrations and with a decrease in plasma glutathione (P<0.01) levels. Fenofibrate caused a significant decrease in serum triglyceride concentration (P<0.0001) associated with a decrease in plasma malondialdehyde (P<0.001) and an increase in plasma PAI-1 (P<0.05) and P-selectin (P<0.05) concentrations. We conclude that simvastatin and fenofibrate interact, by different mechanisms, with oxidative stress, a key factor in the modification of fibrinolysis and endothelial function in Type 2 diabetes.
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PMID:Effect of simvastatin and fenofibrate on endothelium in Type 2 diabetes. 1518 81

The aim of the study was to evaluate skin microvascular reactivity (MVR) and possible influencing factors (fibrinolysis, oxidative stress, and endothelial function) in patients with Cushing's syndrome. Twenty-nine patients with active Cushing's syndrome (ten of them also examined after a successful operation) and 16 control subjects were studied. Skin MVR was measured by laser Doppler flowmetry during post-occlusive (PORH) and thermal hyperemia (TH). Malondialdehyde and Cu,Zn-superoxide dismutase were used as markers of oxidative stress. Fibrinolysis was estimated by tissue plasminogen activator (tPA) and its inhibitor (PAI-1). N-acetyl-beta-glucosaminidase, E-selectin, P-selectin, and ICAM-1 were used as markers of endothelial function. Oxidative stress and endothelial dysfunction was present in patients with hypercortisolism, however, increased concentration of ICAM-1 was also found in patients after the operation as compared to controls (290.8+/-74.2 vs. 210.9+/-56.3 ng.ml(-1), p<0.05). Maximal perfusion was significantly lower in patients with arterial hypertension during PORH and TH (36.3+/-13.0 vs. 63.3+/-32.4 PU, p<0.01, and 90.4+/-36.6 vs. 159.2+/-95.3 PU, p<0.05, respectively) and similarly the velocity of perfusion increase during PORH and TH was lower (3.2+/-1.5 vs. 5.2+/-3.4 PU.s(-1), p<0.05, and 0.95+/-0.6 vs. 1.8+/-1.1 PU.s(-1), p<0.05, respectively). The most pronounced impairment of microvascular reactivity was present in patients with combination of arterial hypertension and diabetes mellitus.
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PMID:Impaired microvascular reactivity and endothelial function in patients with Cushing's syndrome: influence of arterial hypertension. 1722 25


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