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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