Glutathione and Its Redox System in Diabetic Polymorphonuclear Leukocytes

Chari, Suresh; Nath, N.; Rathi, Anshu

doi:10.1097/00000441-198405000-00004

Cited by 59 publications

(16 citation statements)

References 12 publications

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“…A decrease in antioxidant capacity has been observed in the plasma of diabetic patients by several research groups [54,63,[75][76][77][78][79][80][81][82][83][84][85]. In a prospective study, Salonen et al found a decline of plasma RRR-a-tocopherol levels after the onset of type 2 diabetes [86].…”

Section: Which Markers Are Available?mentioning

confidence: 99%

The role of oxidative stress in the onset and progression of diabetes and its complications: asummary of a Congress Series sponsored byUNESCO-MCBN, the American Diabetes Association and the German Diabetes Society

Rösen¹,

Nawroth²,

King

et al. 2001

Diabetes Metab. Res. Rev.

830

513

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SummaryThis review summarises the results and discussions of an UNESCO-MCBN supported symposium on oxidative stress and its role in the onset and progression of diabetes. There is convincing experimental and clinical evidence that the generation of reactive oxygen species (ROI) is increased in both types of diabetes and that the onset of diabetes is closely associated with oxidative stress. Nevertheless there is controversy about which markers of oxidative stress are most reliable and suitable for clinical practice. There are various mechanisms that contribute to the formation of ROI. It is generally accepted that vascular cells and especially the endothelium become one major source of ROI. An important role of oxidative stress for the development of vascular and neurological complications is suggested by experimental and clinical studies. The precise mechanisms by which oxidative stress may accelerate the development of complications in diabetes are only partly known. There is however evidence for a role of protein kinase C, advanced glycation end products (AGE) and activation of transcription factors such as NFkB, but the exact signalling pathways and the interactions with ROI remain a matter of discussion. Additionally, results of very recent studies suggest a role for ROI in the development of insulin resistance. ROI interfere with insulin signalling at various levels and are able to inhibit the translocation of GLUT4 in the plasma membrane. Evidence for a protective effect of antioxidants has been presented in experimental studies, but conclusive evidence from patient studies is missing. Large-scale clinical trials such as the DCCT Study or the UKPDS Study are needed to evaluate the long-term effects of antioxidants in diabetic patients and their potential to reduce the medical and socio-economic burden of diabetes and its complications.

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Section: Which Markers Are Available?mentioning

confidence: 99%

The role of oxidative stress in the onset and progression of diabetes and its complications: asummary of a Congress Series sponsored byUNESCO-MCBN, the American Diabetes Association and the German Diabetes Society

Rösen¹,

Nawroth²,

King

et al. 2001

Diabetes Metab. Res. Rev.

830

513

View full text Add to dashboard Cite

show abstract

“…Glutathione (GSH), an important intracellular antioxidant, is depleted in erythrocytes [1], plasma [2], leucocytes [3], and platelets from human diabetic patients [4] and in endothelial cells from diabetic rabbits [5]. The changes in GSH levels, which result in an oxidant/prooxidant imbalance, may predispose the cells to oxidantinduced damage and diabetic complications.…”

Section: Introductionmentioning

confidence: 99%

Restoration of glutathione levels in vascular smooth muscle cells exposed to high glucose conditions

Powell

Nally

McMaster

et al. 2001

Free Radical Biology and Medicine

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Abstract-Hyperglycemia-induced oxidative stress may play a key role in the pathogenesis of diabetic vascular disease. The purpose of this study was to determine the effects of glucose on levels of glutathione (a major intracellular antioxidant), the expression of ␥-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione de novo synthesis), and DNA damage in human vascular smooth muscle cells in vitro. High glucose conditions and buthionine sulphoximine, an inhibitor of ␥-glutamylcysteine synthetase, reduced intracellular glutathione levels in vascular smooth muscle cells. This reduction was accompanied by a decrease in the mRNA expression of both subunits of ␥-glutamylcysteine synthetase as well as an increase in DNA damage. In high glucose conditions, incubation of the vascular smooth muscle cells with ␣-lipoic acid and L-cystine restored glutathione levels. We suggest that the decrease in GSH levels seen in high glucose conditions is mediated by the availability of cysteine (rate-limiting substrate in de novo glutathione synthesis) and the gene expression of the ␥-glutamylcysteine synthetase enzyme. Glutathione depletion is associated with an increase in DNA damage, which can be reduced when glutathione levels are restored.

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“…1 The increase in adverse cardiovascular outcome associated with hyperglycemia may result from impaired coronary microcirculatory responses to ischemia, 2 increased oxidative stress, 3,4 reduced bioavailability of nitric oxide, 5 and advanced glycation end product formation in the vessel wall and matrix. 6,7 Coronary collateral development is an important adaptive response to reducing myocardial ischemia. Impaired coronary collateral development contributes to the morbidity and mortality associated with CAD.…”

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confidence: 99%

Chronic Hyperglycemia Attenuates Coronary Collateral Development and Impairs Proliferative Properties of Myocardial Interstitial Fluid by Production of Angiostatin

et al. 2004

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Background-Development of coronary collateral vessels is impaired in patients with diabetes mellitus. We tested the hypothesis that hyperglycemia alone attenuates collateral development and abolishes proliferative properties of myocardial interstitial fluid (MIF) by enhancing expression of matrix metalloproteinases (MMP) and angiostatin. Methods and Results-Chronically instrumented dogs were randomly assigned to receive an infusion of normal saline (control; nϭ9) or 70% dextrose in water to increase blood glucose to 350 to 400 mg/dL for 8 h/d (hyperglycemia; nϭ7) in the presence or absence (sham; nϭ9) of brief (2 minutes), repetitive coronary artery occlusions (1/h; 8/d for 21 days). Collateral perfusion increased to 41Ϯ11% and 49Ϯ6% of normal zone flow in control dogs on days 14 and 21 (PϽ0.05) but remained unchanged over 21 days in hyperglycemic and sham dogs (12Ϯ3% and 13Ϯ3%, respectively). A progressive reduction of the postocclusive peak reactive hyperemic response was also observed in control dogs (16Ϯ1 to 10Ϯ1 Hz · 10 2 on days 1 and 21, respectively) but not in hyperglycemic (17Ϯ2 to 20Ϯ2) or sham (17Ϯ2 to 16Ϯ1) dogs. Endothelial cell tube formation was produced by MIF obtained from control dogs but not hyperglycemic or sham dogs. Coincubation of MIF from hyperglycemic dogs with an angiostatin antibody restored endothelial cell tube formation. MMP-9 activity and expression of angiostatin were increased in dogs receiving exogenous glucose compared with controls Conclusions-Chronic hyperglycemia abolishes development of coronary collateral vessels by increasing MMP-9 activity and angiostatin expression in dogs.

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Glutathione and Its Redox System in Diabetic Polymorphonuclear Leukocytes

Cited by 59 publications

References 12 publications

The role of oxidative stress in the onset and progression of diabetes and its complications: asummary of a Congress Series sponsored byUNESCO-MCBN, the American Diabetes Association and the German Diabetes Society

The role of oxidative stress in the onset and progression of diabetes and its complications: asummary of a Congress Series sponsored byUNESCO-MCBN, the American Diabetes Association and the German Diabetes Society

Restoration of glutathione levels in vascular smooth muscle cells exposed to high glucose conditions

Chronic Hyperglycemia Attenuates Coronary Collateral Development and Impairs Proliferative Properties of Myocardial Interstitial Fluid by Production of Angiostatin

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