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Glutathione, Anti-oxidants and Diabetes

Dietary glutathione protects rats from diabetic nephropathy and neuropathy.
Ueno Y, Kizaki M, Nakagiri R, Kamiya T, Sumi H, Osawa T. [J Nutr. 2002 May;132(5):897-900.] The aim of this study was to examine the involvement of oxidative stress in the progression of kidney dysfunction and neuropathy in diabetes and to evaluate the potential usefulness of glutathione (GSH) in diabetes. Diabetic rats were treated with 1 g/100 g GSH as a dietary supplement. GSH significantly suppressed the diabetes-induced increase in urinary 8-hydroxy-2'-deoxyguanosine, one of the markers of oxidative stress. It also prevented the diabetes-induced increases in albumin and creatinine in urine. The diabetes-induced increase in the tail flick reaction time to thermal stimuli also was normalized by treatment with dietary GSH. In conclusion, GSH treatment can beneficially affect STZ-induced diabetic rats, with preservation of in vivo renal and neural function. This suggests a potential usefulness of dietary GSH treatment to reduce diabetic complications.

Glutathione in overweight patients with poorly controlled type 2 diabetes
Aaseth J and Stoa-Birketvedt G.
[Journal of Trace Elements in Experimental Medicine]. 2000; volume 13, number 1, pages 105-111. "Therapeutic trials with antioxidants that can regenerate the intracellular level of GSH [glutathione] are scarce but promising."

Influence of reduced glutathione infusion on glucose metabolism in patients with non-insulin-dependent diabetes mellitus
De Mattia G, Bravi MC, and others. [Metabolism 1998 Aug;47(8):993-7.] "In conclusion, our data support the hypothesis that abnormal intracellular GSH redox status plays an important role in reducing insulin sensitivity in NIDDM patients. Accordingly, intravenous GSH [glutathione] infusion significantly increased both intraerythrocytic GSH/GSSG ratio and total glucose uptake in the same patients."

Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipideaemic, normotensive, patients with non-insulin-dependent diabetes
De Mattia G, Bravi MC and others. [Diabetologia 1998 Nov;41(11):1392-6.] "NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes. Our data indicate that the vascular endothelium is activated in non-insulin dependent diabetes. Antioxidant treatment counterbalanced such endothelial activation. Thus, antioxidant agents might protect against oxidant-related upregulation of endothelial adhesion molecules and slow down the progression of vascular damage in non-insulin dependent diabetes."

Glutathione in human plasma: Decline in association with aging, age- related macular degeneration, and diabetes
Samiec PS, Drews-Botsch C, and others. [Free Radic Biol Med 1998 Mar 15;24(5):699-704.] Analyses of whole blood GSH showed that GSH was significantly lower in diabetic cases compared to the other groups, but did not reveal any difference associated with age or ARMD. In contrast, GSSG in whole blood was significantly higher in the older groups compared to the younger controls. The results suggest that in studies of age-related pathologies, oxidation of GSH may be a more important parameter than a decline in pool size, while in specific pathologies such as diabetes, both oxidation and a decline in pool size may be important.

Intracellular reduced glutathione content in normal and type 2 diabetic erythrocytes: effect of insulin and (-)epicatechin
Rizvi SI, Zaid MA. [J Physiol Pharmacol 2001 Sep;52(3):483-8] Since oxidative stress has been implicated in the development of diabetic complications and GSH plays an important role in protection against oxidative damages, we have studied the in vitro effect of (-)epicatechin and insulin on the reduced glutathione content in normal and type 2 diabetic erythrocytes. The GSH content was significantly lower in type 2 diabetic patients as compared to normal individuals. In vitro insulin treatment resulted in increase in the GSH content in both normal and type 2 diabetic erythrocytes. (-)Epicatechin also resulted in an increase in erythrocyte GSH content in both normal and type 2 diabetic erythrocytes. Although the exact mechanism by which (-)epicatechin causes elevation of erythrocyte GSH is not clear nevertheless this finding may have important therapeutic implications. A higher content of dietary flavanoids may thus protect diabetic patients against long-term complications.

Apoptosis and oxidative status in peripheral blood mononuclear cells of diabetic patients
Graber R, Farine JC, and others. [Apoptosis. 1999; volume 4, number 4, pages 263- 270.]

Hyperglycemia in diabetic rats reduces the glutathione content in the aortic tissue
Tachi Y, Okuda Y, Bannai C, Bannai S, Shinohara M, Shimpuku H, Yamashita K, Ohura K. [Life Sci 2001 Jul 20;69(9):1039-47] The glutathione redox cycle plays a major role in scavenging hydrogen peroxide (H2O2) under physiological conditions. Recently, we demonstrated that a high glucose concentration in the culture medium reduced the level of H2O2 scavenging activity of human vascular smooth muscle cells (hVSMCs). We also showed that a high glucose concentration reduced the intracellular glutathione (GSH) content and the rate of uptake of cystine, which itself is a rate-limiting factor that maintains the GSH level. In the present study, we investigated whether the hyperglycemic condition in diabetic rats impairs the glutathione content in the aortic tissue in vivo. We demonstrated in vivo that the hyperglycemic condition in STZ-induced diabetic Wistar rats and OLETF rats reduced the GSH content in aortic tissue. This suggested reduced glutathione redox cycle function of aorta.

Association of Glutathione Peroxidase Activity with Insulin Resistance and Dietary Fat Intake during Normal Pregnancy
Xinhua Chen, Theresa O. Scholl, Maria J. Leskiw, Melissa R. Donaldson and T. Peter Stein [ The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 12 5963-5968] Glutathione peroxidase (GPx) is one of the most important antioxidant enzymes in humans. We studied the relationship between erythrocyte GPx activity and fasting serum insulin, plasma glucose, and C-peptide, estimates of insulin resistance from the homeostasis model of assessment as well as dietary fat intake in 408 normotensive nondiabetic pregnant women from Camden, NJ. In conclusion, we demonstrated that normal pregnancy is associated with increased GPx activity and insulin resistance. There are ethnic differences in antioxidant response and dietary fat intake. Our findings suggest a potential link among antioxidant defenses, insulin resistance, and dietary fat intake.


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