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)

Depletion of lens glutathione (GSH) occurs quickly and drastically following induction of diabetes or galactosemia in rats as well as in lens culture. The explanation for this dramatic loss of GSH has been investigated by many laboratories but the solution has been elusive. There are several possible causes for the change in the reducing power of the lens under hyperglycemia. (a) The enzyme glutathione reductase which reduces oxidized glutathione to GSH is inhibited. (b) The cofactor NADPH which both the aldose reductase of polyol pathway and glutathione reductase require becomes depleted under hyperglycemia to the point that there is an insufficient amount for glutathione reduction. (c) Membrane permeability is increased, due to osmotic-induced lens hydration. We explored all the above possibilities in the mechanism of GSH depletion and studied the effect of aldose reductase inhibitor (ARI) on osmotic change. We found that under hyperglycemic condition, there was no change in the enzyme glutathione reductase activity. There was an initial drop in NADPH level but there was sufficient remaining for glutathione reductase use. Both NADPH and glutathione depletion could be prevented completely by ARI. In addition, ARI could also prevent any hyperglycemic-induced abnormal transport and leakage of amino acids. We have therefore concluded that only the decreased membrane transport of amino acids which are needed for glutathione biosynthesis and the simultaneous loss of GSH through leaky membrane as initiated by the polyol pathway can be responsible for the drastic GSH depletion.
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PMID:Glutathione depletion in the lens of galactosemic and diabetic rats. 313 35

Streptozotocin (STZ) increased the activity of mouse hepatic glutathione (GSH) S-transferases assayed with 1-chloro-2,4-dinitrobenzene. Nicotinamide administered prior to STZ prevented the hyperglycemia indicative of STZ-induced diabetes, but had no effect on the increase in GSH S-transferase activity caused by the drug. Another diabetogenic agent, alloxan, did not alter GSH S-transferase activity. Thus, streptozotocin may be increasing GSH S-transferase activity directly, and not as a result of the diabetic state the drug induces. Two transferases were characterized from mouse liver cytosol. One was a homodimer with a subunit molecular weight of about 28,000 and a pI of about 8.2. The other was also a homodimer with a subunit molecular weight of about 27,500 and a pI of about 9.2. The pI 8.2 GSH S-transferase was induced by STZ, while the pI 9.2 transferase was decreased by the drug. At least one other transferase appeared to be induced by STZ. Two other nitroso compounds, chlorozotocin and diethylnitrosamine, also increased GSH S-transferase activity, suggesting that this effect may be nitroso related.
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PMID:Effect of streptozotocin on the glutathione S-transferases of mouse liver cytosol. 315 1

In this study we have investigated the oxidative metabolism of red blood cells (RBC), plasma, serum, aqueous humor, and lens of healthy subjects and of age-matched cataractous patients with and without diabetes. Reduced and oxidized glutathione (GSH GSSG) levels in RBC were similar among the three groups. Plasma levels of GSSG were higher in diabetics than in cataractous and control subjects. No differences in plasma content of GSH were noted among the three groups. The activity of the enzyme glucose-6-phosphate dehydrogenase was significantly diminished in diabetic patients. Controls and cataractous patients showed similar levels of malondialdehyde (MDA). Although not significant the MDA content in RBC from diabetics was elevated. No differences in plasma levels of vitamin E were noted among the three groups. The biological liquid oxidant activity of serum in diabetic patients was significantly higher than in controls and cataractous patients. GSH levels in aqueous humor were similar in diabetic and nondiabetic cataractous patients. The content of GSSG in aqueous humor was highest in diabetic patients. Control clear lenses showed low levels of MDA. The MDA levels in cataractous lenses from nondiabetic patients were significantly higher than those of controls. In diabetic patients the content of MDA in the lens was approximately twice as high as the cataractous values. Our results seem to demonstrate that oxidative damage could play a role in the pathogenesis of cataract in diabetes.
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PMID:Systemic human diseases as oxidative risk factors in cataractogenesis. I. Diabetes. 318 3

We investigated the possible involvement of reactive oxygen radical-related processes in chronic (12-wk) diabetes induced in rats by streptozocin (STZ). Diabetes was associated with significantly increased activities of catalase (CAT), glutathione reductase (GSSG-RD), and CuZn-superoxide dismutase (SOD) in the pancreas and of CAT and GSSG-RD in the heart. On the other hand, the liver of diabetic rats showed a generalized decrease in CAT, glutathione peroxidase (GSH-PX), and SOD as well as in the levels of reduced glutathione (GSH). Diabetic kidney also showed decreases in CAT and SOD, but the activities of GSH-PX were increased. Insulin treatment (9-12 U/kg body wt) that was started after 8 wk of diabetes and continued for 4 wk reversed all of the foregoing alterations in tissue antioxidant status. Our results suggest the presence of increased oxidative stress in uncontrolled diabetes as manifested by the marked alterations in tissue antioxidant enzyme activities, the magnitude of which increased with the degree of emaciation. The complex patterns of changes observed in the various tissues examined are believed to be the result of compensatory increases in enzyme activities (usually involving enzymes whose activity in control tissues is low) and direct inhibitory effects, possibly resulting from an increased tissue-oxidant activity. Our findings support the view that tissue antioxidant status may be an important factor in the etiology of diabetes and its complications.
Diabetes 1987 Sep
PMID:Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment. 330 71

Tissue antioxidant status in insulin-dependent spontaneously diabetic BB Wistar rats (ISDBB), diabetes-prone nondiabetic littermates (NDLM), and weight-matched non-BB control Wistar rats was investigated in pancreas, heart, and liver, as well as kidney. Pancreatic activities of CuZn-superoxide dismutase and glutathione reductase (GSSG-RD) were higher in ISDBB rats, while catalase (CAT) activities were elevated in both ISDBB and their NDLM compared with control animals. On the other hand, pancreatic reduced glutathione (GSH) levels were decreased in both ISDBB and NDLM rats. Cardiac tissues of ISDBB rats had higher activities of CAT and GSSG-RD and elevated levels of GSH compared with weight-matched control rats. Hepatic GSH levels in both ISDBB and their NDLM were lower than those of control rats. ISDBB rats showed higher renal activities of glutathione peroxidase compared with control rats. Our results demonstrate the presence of alterations in tissue antioxidant status in BB Wistar rats (both diabetic BB rats and their diabetes-prone nondiabetic littermates). The fact that most of the enzyme changes present in BB rats with overt diabetes paralleled those we have previously reported in rats with uncontrolled streptozotocin-induced diabetes and the fact that the latter alterations were corrected with insulin therapy suggest that the alterations in diabetic BB rats were probably related to suboptimal insulin therapy. The significance of the alterations in antioxidant status seen in the nondiabetic BB animals is as yet unknown.
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PMID:Alterations in tissue antioxidant systems in the spontaneously diabetic (BB Wistar) rat. 332 63

This study was carried out to determine the relationships between blood trace metal concentrations and the clinical status of patients with cerebrovascular disease, gastric cancer and diabetes mellitus. The concentrations of blood trace metals were determined by flameless atomic absorption spectrophotometry. The concentrations were compared to clinical parameters such as blood biochemical parameters, CBC, etc. The contribution of blood trace elements to these three diseases and the possibilities for prophylaxis of these three diseases are discussed. The results obtained were as follow: 1. Patients with cerebrovascular disease showed generally lower concentrations than normal subjects, while the gender difference of the blood metal concentrations showed a pattern similar to that of normal subjects. In some combination, significant correlations were observed between blood metal concentrations and clinical biochemical parameters. 2. As the stage of gastric cancer advanced, blood copper concentrations increased. In all gastric cancer patients the blood copper concentration had a positive correlation with platelet counts, CEA and LDH, and a negative correlation with hemoglobin concentrations, hematocrit value and catalase. Plasma copper concentrations had a significant positive correlation with catalase. Corpuscular zinc concentrations had a significant positive correlation with platelet counts, CEA, ALP and LDH, and a significant negative correlation with hemoglobin concentration and GSH-Px. Corpuscular manganese concentrations had a significant positive correlation with CEA and LDH. 3. The blood copper concentration of patients with diabetes mellitus showed a distribution pattern similar to that of healthy subjects. Therefore, copper is not considered to be an important factor in diabetes mellitus. Diabetic patients treated by insulin injection showed increased blood zinc concentrations. Chromium, which is contained in GTF (glucose tolerance factor), showed lower blood concentrations in patients with severe complications, such as retinopathy or nephropathy. Therefore, it appears that chromium plays an important role in advancing diabetes mellitus.
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PMID:[Studies on the relationships between blood trace metal concentrations and the clinical status of patients with cerebrovascular disease, gastric cancer and diabetes mellitus]. 344 33

A cytochrome has been detected in secretory granules prepared from anglerfish islets of Langerhans. The heme moiety was determined to be of the b type, and the dithionite-reduced cytochrome exhibited an alpha-band maximum at 561 nm with an extinction coefficient of 13.8 mM-1 X cm-1. The protein was present at a concentration of 40 +/- 4 pmol/mg of secretory granule protein. The cytochrome was found to be an integral membrane protein and to be reduced by ascorbic acid but not by NADH, NADPH, reduced glutathione (GSH), or succinate. Because of the similarity to previously characterized secretory granule cytochrome b561's from neuroendocrine tissues, this cytochrome is also referred to as cytochrome b561. Although its function has not yet been elucidated, the apparent specificity for ascorbate suggests that it may be a component of the ascorbate-dependent peptidyl-glycine alpha-amidating monooxygenase system that functions in the amidation of islet hormones.
Diabetes 1986 Aug
PMID:Islet secretory granules contain cytochrome b561. 352 85

It has been established that the pyrogallol autoxidation method for the estimation of the activity of superoxide dismutase (SOD) (EC 1.15.1.1) is superior in precision and sensitivity to a superoxide-generating method (NADH/phenazine methosulfate linked to nitroblue tetrazolium reduction). Reference intervals were established in an urban population in the Far East for SOD activity in erythrocytes using the pyrogallol method, and for glutathione peroxidase (GSH-Px) (EC 1.11.1.9) activity in erythrocytes using a standard glutathione reductase-linked method. On this basis, erythrocyte SOD activities were significantly (P less than 0.05) depressed in cases of visceral cancer, acute myocardial infarct, congestive heart failure, respiratory failure, chronic renal failure, and diabetes mellitus, but within the reference interval in cases of lung cancer and asthma. Erythrocyte GSH-Px activity was significantly (P less than 0.05) depressed in cases of diabetes mellitus and chronic renal failure but elevated in respiratory failure and asthma. GSH-Px and SOD activities were well correlated in patients but not in the reference population.
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PMID:Superoxide dismutase and glutathione peroxidase activities in erythrocytes as indices of oxygen loading in disease: a survey of one hundred cases. 366

The activities of three drug conjugation reactions, glutathione, glucuronic acid and sulphate conjugation and the synthesis of glutathione, have been measured in hepatocytes isolated from streptozotocin-induced male diabetic rats. The intracellular content of reduced glutathione (GSH) was decreased in diabetic rat hepatocytes compared with controls. Following depletion of the intracellular GSH stores with diethylmaleate, the resynthesis of GSH in the presence of 0.5 mM L-methionine, occurred faster in diabetic rat hepatocytes than in those from control rats indicating that the cystathione pathway may be more efficient in the diabetic animals. In contrast, there was no significant difference in the resynthesis of GSH between control and diabetic rat hepatocytes in the presence of L-cysteine. The GSH conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and 3,4-dichloronitrobenzene (DCNB) was deficient in diabetic rat hepatocytes, although only the effect on the former reaction was statistically significant (P less than 0.05). The Vmax for CDNB conjugation was significantly lower (P less than 0.05) in cytosolic fractions prepared from diabetic rat liver than in control rat liver fractions. This was accompanied by an increase in the affinity of the enzyme for CDNB. In contrast, the Vmax and Km for the conjugation of DCNB in cytosolic fractions were unaffected by the induced-diabetes. Glucuronic acid conjugation of both 1-naphthol and phenolphthalein was markedly deficient in diabetic rat hepatocytes. The intracellular concentrations of the cofactor for glucuronidation, UDP-glucuronic acid, were decreased in diabetic rat liver and this was thought to contribute to the defect in glucuronidation. The sulphation of 1-naphthol was not significantly altered by the induced diabetes. Deficiencies in glutathione and glucuronic acid conjugation in streptozotocin-induced diabetic rats may result in an increased susceptibility to xenobiotic induced cytotoxicity.
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PMID:Conjugation reactions in hepatocytes isolated from streptozotocin-induced diabetic rats. 367 22

Alterations in endogenous free radical-scavenging defense mechanisms of rat tissues after body weight loss (induced by starvation for 72 h) associated with hypoinsulinemia were investigated. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione (GSSG) reductase as well as levels of reduced glutathione (GSH) were examined in several tissues and in erythrocytes. A complex pattern of changes was observed. CAT activities were increased in the heart and pancreas and decreased in the liver. SOD levels were decreased in the heart and increased in the kidney and pancreas. GSH-PX activities were increased only in the kidney, and levels of GSH were decreased only in the liver of starved animals. Erythrocytes from starved animals showed no alterations in the levels of major free radical-scavenging enzymes. However, GSSG reductase levels were lower in erythrocytes from starved animals, and this was associated with an increased susceptibility to H2O2-induced GSH depletion. Paradoxically, H2O2-induced malondialdehyde (MDA) production in erythrocytes from starved animals was lower than that in control erythrocytes. Our results suggest that, in studies of experimental diabetes, attention must be given to the influence of body weight loss per se on the biochemical alterations associated with this disease.
Diabetes 1987 Feb
PMID:Starvation-related alterations in free radical tissue defense mechanisms in rats. 380 31


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