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)

Severe resistance to subcutaneous insulin but sensitivity to intravenous insulin persisted for 15 months in a 17-year-old diabetic girl. Heat-labile insulin-degrading activity was present in the patient's ketotic sera and in the 100,000 g fraction (soluble fraction) of adipose tissue. Serum-degrading activity was not inhibited by N-ethylmaleimide. The soluble fraction also degraded glucagon and B chain but not growth hormone or myoglobin. It was inhibited by incubation with the patient's nonketotic sera, normal sera, or Trasylol. Glutathione-insulin-transhydrogenase (GIT) activity was 66% of normal. The biopsy of adipose tissue at remission showed a normal level of insulin- and glucagon-degrading activity. The activity was eluted from Sephadex G200 as a single peak and had properties consistent with those of the insulin-specific protease (ISP). The increased degrading activity present during insulin resistance had properties not shared with ISP, suggesting the presence of an uncharacterized protease.
Diabetes 1979 Jul
PMID:Insulin resistance caused by massive degradation of subcutaneous insulin. 10 40

The degradation of insulin by isolated rat liver cells has been studied. The phenomenon is time- and temperature-dependent. After sixty minutes' exposure to 1.5 times 10-6 cells/ml, about 50 per cent, 15 per cent, and less than 5 per cent of insulin at 1.5 muM. are degraded at 37 degrees C., 20 degrees, and 0 degrees C., respectively. The methods used to measure the hormone degradation effect the apparent Vmax. Higher values of Vmax are found when radioimmunoassay rather than precipitation by trichloracetic acid and absorption to talc is used. However, the apparent Km. (0.27 muM) is virtually the same with any of methods used. N-ethyl-maleimide and Trasylol are potent inhibitors, whereas GSH increases the hormone degradation. Proinsulin acts as competitive inhibitor (apparent Ki equals 0.35 muM.). Gel filtration patterns of incubation supernates suggest that several enzymatic systems may be operative in the degradation of insulin by the liver cells. Glutathione-insulin-transhydrogenase is suggested by the appearance of a component that has the same elution volume as the A chain, but the inhibitory effects of trasylol on insulin degradation, as well as qualitative and quantitative similarities with insulin proteases, suggest that a proteolytic similiarities with insulin proteases, suggest that a proteolytic mechanism is involved. The insulin-degrading system in isolated liver cells closely resembles that observed in purified liver plasma membranes and in the isolated perfused liver. Such similarities stress the possible significance of the degradation process in the regulation of insulin action. These studies are also important for the quantitative analysis of insulin interaction with its specific receptors in isolated liver cells.
Diabetes 1975 Jun
PMID:Degradation of insulin by isolated rat liver cells. 16 96

This study deals with investigations in diabetic disorders. Experiments were carried out on alloxan-induced diabetes in albino rats. Blood glucose, keto acids, and glutathione were determined before and after induction of alloxan diabetes. Blood glucose and keto acids showed an increase after administration of alloxan. Glutathione showed a drop after 1/2 hour, then began to increase till it reached its normal level after 48 hours from the beginning of the diabetic state. The results are discussed.
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PMID:Blood glucose, glutathione, and total keto-acids levels in alloxan-diabetic rats. 60 26

Changes in the levels of lipid peroxides and antioxidant enzymes were studied in male albino rats with experimental diabetes mellitus. Diabetes was induced by single subcutaneous injection of alloxan (19 mg/100 g body weight). The concentration of malondialdehyde (MDA) showed an increase both in the liver (P less than 0.01) and kidney (0 less than 0.05), while in the heart, there was a decrease (P less than 0.01), as compared to control values. A similar pattern of change was observed in the level of hydroperoxides in the liver and heart. The conjugated dienes showed an elevation during diabetes in all tissues (P less than 0.01). Glutathione levels in heart (P less than 0.01) and kidney were found to be decreased (P less than 0.05) while the liver showed an elevation during long-term diabetes (P less than 0.01). Serum ceruloplasmin showed an increase (P less than 0.05) in diabetes. Antioxidant enzymes superoxide dismutase and catalase decreased in all tissues (P less than 0.01) while the activity of glutathione s-transferase increased in heart, but no change in other tissues. The studies thus show that lipid peroxidation is activated in liver and kidney while heart tissues show some resistance towards lipid peroxidation.
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PMID:Peroxidative changes in experimental diabetes mellitus. 151 41

Studies were carried out on the metabolism of lipid peroxides and antioxidative enzymes during diabetes and diabetes superimposed with myocardial infarction. Diabetes was induced using alloxan and myocardial infarction was induced by isoproterenol. In the case of diabetic animals there was a decrease in the levels of lipid peroxides in the heart while in the case of diabetes associated with myocardial infarction it was slightly elevated. The activity of superoxide dismutase and catalase showed a decrease in both the groups. Glutathione showed a fall in the case of diabetes and diabetes associated with myocardial infarction while taurine in heart and ceruloplasmin in the serum was elevated. Histopathological changes in the heart tissue showed some focal changes in the case of both diabetes and diabetes associated with myocardial infarction, but the degree of necrosis was much less than in the case of myocardial infarction.
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PMID:Changes in levels of lipid peroxides and activity of superoxide dismutase and catalase in diabetes associated with myocardial infarction. 152 61

Glutathione is important in the regulation of the redox state, and a decline in its tissue level has often been considered to be indicative of increased oxidative stress in diabetes. In this study of diabetic rats, the level of hepatic glutathione was normal unless food intake was restricted. Thus, the previous report of a reduction in hepatic glutathione in diabetes is likely to be the result of food deprivation rather than diabetes alone. In contrast to changes characteristic of oxidative stress, the efflux of glutathione in bile from diabetic animals was significantly decreased, whereas hepatic mixed disulfides were unchanged, and the hepatic gamma-glutamyltransferase activity was considerably increased. These changes were not reproduced by food deprivation. The decrease in biliary excretion of glutathione in diabetes may reflect an attempt to conserve glutathione by activation of the hepatic gamma-glutamyl cycle. We conclude that the disturbances of glutathione metabolism in diabetes are not typical of those seen in oxidative stress or food restriction.
Diabetes 1991 Mar
PMID:Changes in hepatic glutathione metabolism in diabetes. 167 44

Cataract is a long-term complication of diabetes mellitus. Diabetics have increased glucosamine levels and it is possible that the non-enzymic glycosylation of the lens structural proteins by glucosamine induces conformational changes in the lens that contribute to cataract formation. Aspirin and aspirin-like analgesics may protect against glycosylation. In this paper the binding of glucosamine to bovine lens proteins and the effects of aspirin, paracetamol and ibuprofen on this reaction were investigated. Significant binding of glucosamine to the lens proteins was found. Gel-chromatography indicated that beta H-crystallin was most reactive to the amino-sugar. Of the analgesics studied, aspirin was the most effective inhibitor of glycosylation, followed by the other anti-inflammatory drug, ibuprofen. Preincubation of the lens homogenate with aspirin was no more effective at decreasing binding of glucosamine than was simultaneous incubation with aspirin. Glutathione significantly inhibited glucosamine binding. Glucosamine is active in non-enzymic glycosylation but the reaction can be inhibited by agents thought to protect against cataract.
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PMID:The non-enzymic glycosylation of bovine lens proteins by glucosamine and its inhibition by aspirin, ibuprofen and glutathione. 275 89

Tissue antioxidant status may be compromised under conditions of dietary restriction, either as the result of a deficiency in a specific cofactor required by a particular antioxidant enzyme or of more complex alterations of a generalized nature triggered by metabolic responses to starvation. Many similarities exist between insulin-reversible abnormalities in tissue antioxidant enzyme activities seen in experimental diabetes and in animals subjected to food deprivation-induced weight loss which is associated with hypoinsulinemia. The complex alterations in tissue antioxidant enzyme activities resulting from nutritional deficiency states, disease or drug administration may have important clinical consequences. Free radical-related processes have been implicated in the pathology of certain conditions in which weight loss is frequently recommended (e.g., diabetes and atherosclerosis). It will be important to investigate the possible adverse effects of this intervention on the underlying disease process involved. Glutathione-dependent hepatic detoxification processes are impaired under conditions of nutritional deficiency. This finding not only has important clinical implications but the standard practice of fasting small laboratory animals overnight to ensure reliable drug absorption can markedly influence the results of pharmacological/toxicological experiments. Further studies of the influence of nutritional status on free radical-related processes are likely to yield valuable information which may be applicable to a variety of research and clinical problems.
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PMID:Nutritional deficiency, starvation, and tissue antioxidant status. 307 49

Glutathione functions to scavenge oxidants or xenobiotics by covalently binding them and transporting the resulting metabolites through an adenosine 5'-triphosphate-dependent transport system. It has been reported that the intracellular concentration of glutathione decreases in diabetes mellitus. In order to elucidate the physiological significance and the regulation of anti-oxidants in diabetic patients, changes in the activity of the glutathione-synthesizing enzyme, gamma-glutamylcysteine synthetase, and transport of thiol [S-(2,4-dinitrophenyl)glutathione] were studied in erythrocytes from patients with non-insulin-dependent diabetes and K562 cells cultured with 27 mmol/l glucose for 7 days. The activity of gamma-glutamylcysteine synthetase, the concentration of glutathione, and the thiol transport were 77%, 77% and 69%, respectively in erythrocytes from diabetic patients compared to normal control subjects. Treatment of patients with an antidiabetic agent for 6 months resulted in the restoration of gamma-glutamylcysteine synthetase activity, the concentration of glutathione, and the thiol transport. A similar impairment of glutathione metabolism was observed in K562 cells with high glucose levels. The cytotoxicity by a xenobiotic (1-chloro-2,4-dinitrobenzene) was higher in K562 cells with high glucose than in control subjects (50% of inhibitory concentration 300 +/- 24 mumol/l vs 840 +/- 29 mumol/l, p < 0.01). Expression of gamma-glutamylcysteine synthetase protein was augmented in K562 cells with high glucose, while enzymatic activity and expression of mRNA were lower than those in the control subjects. These results suggest that inactivation of glutathione synthesis and thiol transport in diabetic patients increases the sensitivity of the cells to oxidative stresses, and these changes may lead to the development of some complications in diabetes mellitus.
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PMID:Weakened cellular scavenging activity against oxidative stress in diabetes mellitus: regulation of glutathione synthesis and efflux. 771 15

This study examined the association of blood glutathione level, a potential marker of physiological/functional aging, with a number of biomedical/psychological traits in a subgroup (N = 33) of a representative sample of community-based elderly. Higher glutathione levels were associated with fewer number of illnesses (p < 0.05), higher levels of self-rated health (p < 0.01), lower cholesterol (p < 0.05), lower body mass index, and lower blood pressures. Subjects with diagnoses of arthritis, diabetes, or heart disease (as assessed by physicians) had at least marginally significant lower glutathione levels than those who were disease free. Glutathione, together with age and a measure of suppressed anger, accounted for 39% of the variance of an index of morbidity. Glutathione, by itself, accounted for 24% of the variance. To our knowledge, this is the first evidence of an association of higher glutathione levels with higher levels of physical health in a sample of community-based elderly. Further studies in large samples are needed to investigate glutathione as a potential overall health risk factor for morbidity among the elderly.
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PMID:Glutathione and morbidity in a community-based sample of elderly. 773 Sep 4


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