Evidence for Accelerated Rates of Glutathione Utilization and Glutathione Depletion in Adolescents With Poorly Controlled Type 1 Diabetes

Abstract

Depletion of glutathione, an important antioxidant present in red cells, has been reported in type 1 diabetes, but the mechanism of this depletion has not been fully characterized. Glutathione depletion can occur through decreased synthesis, increased utilization, or a combination of both. To address this issue, 5-h infusions of L-[3,3-2 H 2 ]cysteine were performed in 16 diabetic adolescents divided into a well-controlled and a poorly controlled group and in eight healthy nondiabetic teenagers as control subjects (HbA 1c 6.3 ؎ 0.2, 10.5 ؎ 0.6, and 4.8 ؎ 0.1%, respectively). Glutathione fractional synthesis rate was determined from 2 H 2 -cysteine incorporation into blood glutathione. We observed that 1) erythrocyte cysteine concentration was 41% lower in poorly controlled patients compared with well-controlled patients (P ‫؍‬ 0.009); 2) erythrocyte glutathione concentration was ϳ29% and ϳ36% lower in well-controlled and poorly controlled patients compared with healthy volunteers; and 3) the fractional synthesis rate of glutathione, although similar in well-controlled and healthy subjects (83 ؎ 14 vs. 82 ؎ 11% per day), was substantially higher in the poorly controlled group (141 ؎ 23% per day, P ‫؍‬ 0.038). These findings suggest that in diabetic adolescents, poor control is associated with a significant depletion of blood glutathione and cysteine, due to increased rates of glutathione utilization. This weakened antioxidant defense may play a role in the pathogenesis of diabetes complications. Diabetes

Glutathione Synthesis Rates in Early Postnatal Life

“…The ranges are not caused by outliers but are caused by variation of glutathione FSR within the population. Although the range of fractional synthesis rates is between 30 and 70%/d, the SD is low in both groups compared with similar studies conducted by others (8,39,40).…”

“…GSH is a tripeptide consisting of the amino acids (AA) glutamate, cysteine, and glycine. It is synthesized in virtually every tissue but is mainly produced in liver and erythrocytes with erythrocytic concentrations being in the millimolar range (8). Erythrocytes are suggested to function as antioxidant defense by being a physiologic source of GSH and by taking up ROS (9,10).…”

Histopathological and Immunohistochemical Study of Antidiabetic Effects of Heracleum persicum Extract İn Experimentally Diabetic Rats

“…GPx depletion may have a major role in the pathogenesis of vascular complications and microalbuminuria with increased oxidative stress. 36 In a study by Yoshimura et al 37 GPx was found to be localized diffusely in the cytoplasm of hepatocytes in the liver of rats. Additionally, periportal area had more intense staining than the centriobular area, and no staining was reported in endothelial cells around the sinusoids and in Kupffer cells.…”

Protective Effects of Bryonia multiflora Extract on Pancreatic Beta Cells, Liver and Kidney of Streptozotocin-Induced Diabetic Rats: Histopathological and Immunohistochemical Investigations

“…Decrease of GPx levels, which is among antioxidant enzymes, is thought to be occurred due to inactivation of antioxidant enzymes as a result of glycation caused by hyperglycemia in diabetes. 42 GPx depletion may have a major role in the pathogenesis of vascular complications and microalbuminuria with increased oxidative stress. 43 In a study by Yoshimura et al 44 GPx was found to be localized diffusely in the cytoplasm of hepatocytes in the liver of rats.…”