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

Accelerated atherosclerotic vascular disease is the leading cause of mortality in patients with diabetes mellitus. Endothelium-derived nitric oxide (NO) is a potent endogenous nitrovasodilator and plays a major role in modulation of vascular tone. Selective impairment of endothelium-dependent relaxation has been demonstrated in aortas of both nondiabetic animals exposed to elevated concentrations of glucose in vitro and insulin-dependent diabetic animals. The impaired NO release in experimentally induced diabetes may be prevented by a number of antioxidants. It has been hypothesized that oxygen-derived free radicals (OFR) generated during both glucose autoxidation and formation of advanced glycosylation end products may interfere with NO action and attenuate its vasodilatory activity. The oxidative injury may also be increased in diabetes mellitus because of a weakened defense due to reduced endogenous antioxidants (vitamin E, reduced glutathione [GSH]). A defective endothelium-dependent vascular relaxation has been found in animal models of hypertension and in hypertensive patients. An imbalance due to reduced production of NO or increased production of free radicals, mainly superoxide anion, may facilitate the development of an arterial functional spasm. Treatment with different antioxidants increases blood flow in the forearm and decreases blood pressure and viscosity in normal humans; vitamin E inhibits nonenzymatic glycosylation, oxidative stress, and red blood cell microviscosity in diabetic patients. Long-term randomized clinical trials of adequate size in secondary and primary prevention could support the free-radical hypothesis for diabetic diabetic vascular complications and the use of antioxidants to reduce the risk of coronary heart disease.
 ...
PMID:Diabetes mellitus, hypertension, and cardiovascular disease: which role for oxidative stress? 788 82

Selenium and the selenium-dependent glutathione peroxidase (GSH-Px) were measured in healthy and diabetic children from Germany and Hungary. Hyperglycemia and hyperlipidemia are present in diabetes mellitus and they are associated with increased lipid peroxidation. The selenium content of erythrocytes, whole blood and plasma, as well as of plasma glutathione peroxidase activity, were found to be low in the healthy Hungarian children compared to the healthy Germans. Both groups of diabetics had significantly higher blood selenium (1.05 +/- 0.14 versus 0.86 +/- 0.1 mumol/L in Hungarians, 1.34 +/- 0.21 versus 1.12 +/- 0.22 mumol/L in Germans) and higher plasma selenium (0.89 +/- 0.15 versus 0.68 +/- 0.01 mumol/L in Hungarians and 1.01 +/- 0.2 versus 0.88 +/- 0.19 mumol/L in Germans) than the healthy children of the same countries. In all diabetic children the plasma glutathione peroxidase activity and triglycerides were higher and the plasma HDL-cholesterols (HDLC = high density lipoprotein-cholesterol) lower than those in healthy controls. The patients showed linear correlations between blood glucose and plasma glutathione peroxidase activity, as well as in erythrocyte glutathione peroxidase activity with triglycerides (TG) and an inverse correlation with HDL-cholesterol. Plasma selenium correlated only in healthy children with triglycerides, cholesterol and HDL-cholesterol. Irrespective of the geographical region diabetics had a higher selenium status than healthy children. In addition, we found correlations between selenium and lipoproteins in the reference group. The mode of glycation, oxidative procedures and the selenium binding to lipoproteins could explain the different associations in the healthy and diabetic children.
 ...
PMID:Selenium status and lipoproteins in healthy and diabetic children. 801 49

Diabetic human patients and laboratory animals show abnormalities which can be observed also in enhanced lipid peroxidation (LPO) induced in vitro. It seemed to be necessary to demonstrate the presence of these processes also in dogs with experimentally induced alloxan diabetes. In a 5-day experiment, five 1 to 5-year-old dogs of mixed sex were examined. Blood samples were taken before the intravenous administration of 60 mg alloxan/kg body mass and then daily for a period of 5 days. After the administration of alloxan, the dogs became depressed and lost their appetite. Their urine contained varying concentrations of glucose detectable with a test strip. As compared to the physiological values, blood glucose concentration increased considerably throughout. Alanine aminotransferase (ALT) enzyme activity underwent an 8-fold increase by the 24th hour; subsequently, it remained practically unaltered. The malonyldialdehyde (MDA) concentration of red blood cell (RBC) haemolysate also rose with respect to the basal values. Glutathione-peroxidase (GSH-Px) activity increased only transiently, up to the second day of the experiment; subsequently, its activity dropped below the basal values. Similar changes were found in catalase activity, while the activity changes of superoxide dismutase (SOD) were identical in tendency to the above ones; in fact, it hardly showed any alterations. Besides the severe pancreatic and liver damage caused by alloxan, increased MDA production in the RBC haemolysate indicated enhanced peroxidation of polyunsaturated fatty acids, i.e. intensification of the LPO processes. The increase of GSH-Px and catalase activity, followed by their decrease was suggestive of changes in the enzymatic defence mechanism acting against free radicals.
 ...
PMID:Changes of lipid peroxidation parameters in dogs with alloxan diabetes. 806 47

The effects of vanadyl sulfate treatment on susceptibility to oxidative stress were investigated in streptozotocin-diabetic Wistar rats. A 2 x 2 factorial design was employed, with four groups of animals: 1) untreated, non-diabetic; 2) vanadyl-treated, non-diabetic; 3) untreated, diabetic; and 4) vanadyl-treated, diabetic. Vanadyl sulfate was administered as a 1.00 to 1.25 mg/ml solution in drinking water. Cataract development was entirely suppressed in vanadyl-treated compared to untreated, diabetic rats. STZ-induction of diabetes diminished glutathione (GSH) levels in liver homogenates; whereas vanadyl treatment resulted in restored levels of this nonenzymatic antioxidant. Thiobarbituric acid reactive substances (TBARS), both basal and iron-stimulated, were significantly elevated in all vanadyl-treated animals. Vanadyl treatment lowered liver glutamine synthetase activities in diabetic rats, but not in non-diabetic animals. Thus, vanadyl treatment was antioxidant in terms of cataract formation and reduced glutathione concentration in liver homogenates, pro-oxidant by reason of iron-stimulated TBARS formation and inconclusive with respect to glutamine synthetase activity. These results highlight the importance of using multiple indicators of peroxidative change in evaluating new pro-oxidant/antioxidant treatment regimens.
 ...
PMID:Effect of vanadyl sulfate feeding on susceptibility to peroxidative change in diabetic rats. 810 Jun 38

We designed this study to examine whether uncontrolled hyperglycemia, duration of diabetes, or race (black v white) have any effect on glutathione levels in erythrocytes of type I diabetic patients. Hyperglycemia was assessed by measuring the level of hemoglobin A1c (HbA1c). Results show that erythrocytes of diabetic patients have a significantly lower glutathione level compared with those of age-matched normal subjects (P < .004). We found a significant negative correlation (r = -.59, P < .001) between the degree of hyperglycemia and the level of reduced glutathione (GSH) in erythrocytes of diabetic patients. There was no significant relationship (r = -.29, P > .12) between the level of GSH in erythrocytes and the duration of diabetes. Erythrocytes of black diabetic patients had significantly lower levels of GSH (P < .05) than those of white diabetic patients. Using erythrocytes as a model, this study suggests that a lower level of GSH may have a role in the cellular damage and impaired insulin secretion in uncontrolled diabetic patients.
 ...
PMID:Effect of glycemic control, race (white versus black), and duration of diabetes on reduced glutathione content in erythrocytes of diabetic patients. 813 78

61 spa patients, predominantly with heart and vascular diseases, were divided into 2 therapeutic groups. In addition to the usual balneotherapeutic program, one group (J) received a course of "iodine brine concentrate" for drinking (2 x 100 ml, daily iodine uptake approximately 9 mg), and the control group (CI) received isotonic NaCl in the same way. The patients were mostly on a reduced-fat and -calorie diet. The following parameters were determined at the beginning and at the end of the 26-day treatment period: total cholesterol, HDL-cholesterol, triglycerides, lipoprotein (a) (in serum); selenium (Se), malondialdehyde (MDA), and activities of Se-dependent, Se-independent, and total glutathione peroxidase (GSH-PX) (in plasma). In the J group, a significant increase was found in Se-independent (+17%) and total GSH-PX (+5%) and a significant decrease in total cholesterol (-6.9%) and MDA (-13.2%). At the end of the cure, Se levels were higher in the J group than in the C1 group. The only significant change in the C1 group was a decrease in HDL-cholesterol. Positive correlations were found between selenium and Se-dependent GSH-PX (r = 0.253) and between total GSH-PX and Se-dependent GSH-PX (r = 0.665). A negative correlation was obtained between Se-dependent and Se-independent GSH-PX (r = -0.331). The results are discussed with regard to the importance of antioxidant defense mechanisms in several degenerative diseases (atherosclerosis, diabetes, cataract etc.), and also respecting interactions between iodine and selenium metabolism, as well as normalization effects conditioned by the balneotherapy itself.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Changes in selenium status, antioxidant enzyme activity and lipid peroxide level after drinking cures in Bad Hall health resort]. 814 96

To determine whether increased oxidative stress in diabetes mellitus is due to an impaired free-radical scavenger function in endothelial cells, GSH-dependent H2O2 degradation in human umbilical vein endothelial cells was studied. The GSH-dependent, NaN3-uninhibitable H2O2-degradation in endothelial cells was reduced by 48% (p < 0.001) when the cells were exposed to 33 mmol/l D-glucose vs 5.5 mmol/l D-glucose. This impairment was dependent not only on the D-glucose concentration in the medium but also on D-glucose specific metabolism, since neither 27.5 mmol/l L-glucose nor 27.5 mmol/l D-raffinose had any effect on the peroxide degradation activity. Activation of the glutathione redox cycle by H2O2 in cells exposed to high glucose concentrations was attenuated as compared with 5.5 mmol/l D-glucose because of: 1) a 42% decrease (p < 0.001) in intracellular NADPH content, and 2) a 34% reduction (p < 0.01) in glutathione release into the media. This results in an accumulation of GSSG in the cells following exposure to H2O2. Both H2O2-evoked 51Cr-release and H2O2-induced endothelial cell damage were significantly (p < 0.01) greater in the 33 mmol/l D-glucose group than in the 5.5 mmol/l D-glucose group. These results indicate that the abnormal glutathione redox cycle observed in endothelial cells is induced by high glucose concentrations in the medium, resulting in an impairment of reduced GSH-dependent H2O2-degradation. These abnormalities may associate with the increased cellular damage following an exogenous exposure to H2O2.
 ...
PMID:Abnormal glutathione metabolism and increased cytotoxicity caused by H2O2 in human umbilical vein endothelial cells cultured in high glucose medium. 817 40

Levels of lipid peroxidation in liver, kidney, brain and blood, liver glutathione (GSH) and several enzymes in liver tissue associated with antioxidant defence mechanism, namely Catalase (EC: 1.11.1.6), GSH reductase (EC:1.6.4.2) and GSH-S-transferase (EC: 2.5.1.18), were investigated in streptozotocin-induced diabetic rats. The single intraperitoneal injection of streptozotocin (65 mg/kg) caused a four-, eight- and seven-fold increase in lipid peroxidation in brain, liver and kidney, respectively. A decline in GSH levels both in blood (two-fold) and liver (16%) compared with normal counterparts was also observed. A marginal increase in catalase activity, a 20% decrease in GSH reductase and an increase of GSH-S-transferase activity was also found in this experimental diabetic condition. These results suggest experimental diabetes, induced by streptozotocin, can produce biochemical changes not only in pancreas but also in liver, kidney and brain tissue.
 ...
PMID:Lipid peroxidation, glutathione levels and changes in glutathione-related enzyme activities in streptozotocin-induced diabetic rats. 820 Jun 86

Streptozotocin diabetes induces a 4-fold increase in the maximal velocity of inner medullary aldose reductase as determined in vitro but increases sorbitol synthesis in intact inner medullary collecting duct (IMCD) cells only 1.3-fold. In order to resolve this discrepancy we investigated the importance of intracellular factors in controlling the role of cellular sorbitol synthesis. These factors include glucose concentration, sorbitol concentration, the activity of the NADPH-regenerating pentose phosphate pathway, intracellular NADP and NADPH content, and intracellular reduced (GSH) and oxidized glutathione (GSSG). It was found that the apparent Km of cellular sorbitol production for glucose was identical in control and diabetic rats (56 +/- 18 vs. 59 +/- 14 mmol/l D-glucose), whereas Vmax increased by 31% in diabetes. In inner medullary collecting duct cells of diabetic rats containing 146 +/- 5 mumol sorbitol/g protein, sorbitol synthesis was slightly lower (-15%), compared to cells which had been sorbitol-depleted prior to the experiment (87 +/- 4 mumol sorbitol/g protein). However, no inhibitory effect of sorbitol (up to 200 mmol/l) was observed on aldose reductase activity in vitro. In diabetic rats the content of NADPH was about 32% lower than in the control rats (3.8 +/- 0.3 vs. 5.6 +/- 0.4 mumol/g protein) and the ratio of NADPH/NADP was decreased from 25.6 +/- 5.1 to 8.6 +/- 1.7. In homogenates of the inner medulla the activity of 6-phospho-gluconate dehydrogenase (EC 1.1.1.43) was identical in both experimental groups, so the pentose phosphate shunt seems to be unaltered. GSH content in diabetic rats was also diminished (4.02 +/- 0.67 mumol/g protein vs. 7.41 +/- 0.5 mumol/g protein) and the GSH/GSSG ratio fell from 92.6 to 57.4. In enzyme tests in vitro an apparent Km of 7.3 +/- 1.9 mumol/l of the aldose reductase for NADPH was found; NADP acted as competitive inhibitor with an apparent K(i) of 183 +/- 31 mumol/l. Aldose reductase activity was also found to be strongly inhibited by the SH-group reagent p-chloromercurybenzoesulfonate (apparent K(i) = 0.85 x 10(-6) mol/l). Combining the results obtained on the properties of the aldose reductase in vitro and the observation made in the intact cells, the investigators suggest that the decrease in NADPH/NADP ratio, as well as changes in the redox state in the cells of diabetic animals, can play a significant role in the control of sorbitol synthesis.
 ...
PMID:Control of sorbitol metabolism in renal inner medulla of diabetic rats: regulation by substrate, cosubstrate and products of the aldose reductase reaction. 824 Dec 88

The effect of sodium metavanadate (NaVO3) consumption on trace element metabolism, components of the antioxidant defense system and lipid oxidative damage were studied in control (CON) and streptozotocin-induced diabetic (DIAB) rats. Ten days after injection, CON and DIAB rats received either 0 mM NaVO3/80 mM NaCl (0 group) or 1.2 mM NaVO3/80 mM NaCl (1.2V group) in their drinking water. DIAB groups had higher food and fluid intakes than the CON groups; vanadium (V) groups had lower food and fluid intakes than the saline groups. Vanadium therapy lowered plasma glucose concentrations of DIAB rats. The following parameters were similar among the groups: plasma Zn, Cu and Fe concentrations, plasma ceruloplasmin activity, liver Zn, Cu, Mn and Fe concentrations, kidney Mn and Fe concentrations, liver non-Se-dependent glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Red) and Mn-SOD activities, liver reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations and kidney non-Se-dependent GSH-Px activity. Kidney Zn and Cu concentrations were higher in DIAB rats than in CON rats. The CON-1.2V and DIAB-1.2V groups had V accumulation in the liver and kidney. Liver CuZn-SOD and Se-dependent GSH-Px and kidney CuZn-SOD and GSH-Red activities were lower in DIAB rats compared to CON rats; kidney Mn-SOD and kidney Se-dependent GSH-Px activities were higher in DIAB rats than CON rats. Vanadium treatment did not cause significant alterations in the antioxidant defense system; however, tissue vanadium concentrations were positively correlated to TBARS production. These results show that diabetes caused significant alterations in the antioxidant defense system and that V therapy was associated with a marked deterioration in health of both control and diabetic rats.
 ...
PMID:Vanadium treatment of diabetic Sprague-Dawley rats results in tissue vanadium accumulation and pro-oxidant effects. 824 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>