Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1802, Issue 11, Pages 942-951Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2010.07.001
Keywords
Cortex; Hippocampus; Hyperglycemia; Insulin-induced hypoglycemia; Mitochondria; Oxidative stress
Funding
- Portuguese Foundation for Science and Technology [SFRH/BD/43968/2008]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/43968/2008] Funding Source: FCT
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This study was undertaken to evaluate the effects of streptozotocin (STZ)-induced hyperglycemia and insulin-induced hypoglycemia in cortical and hippocampal mitochondria bioenergetics and oxidative status. For that purpose we used, citrate (vehicle)-treated Wistar rats, STZ-treated rats [i.p., 50 mg/kg body weight] and STZ-treated rats injected with insulin [s.c., dose adjusted to blood glucose levels] 1 h prior to sacrifice to induce an acute episode of hypoglycemia Several parameters were analyzed. respiratory chain. phosphorylation system, thiobarbituric acid reactive substances (TBARS) levels. hydrogen peroxide (H2O2) production rate, and non-enzymatic and enzymatic antioxidant defenses. Cortical mitochondria from insulin-induced hypoglycemic rats present a significant decrease in the ADP/0 index, a significant increase in the repolarization lag phase and a decrease in GSH/GSSG ratio when compared with STZ and control mitochondria Both STZ-induced diabetes and insulin-induced hypoglycemia promote a significant increase in TBARS levels and a decrease in glutathione disulfide reductase activity Diabetic cortical mitochondria present a significant decrease in glutathione peroxidase (GPx) activity compared to control mitochondria. In turn. insulin-induced hypoglycemia induced a significant increase in GPx and manganese superoxide dismutase (MnSOD) activities. In hippocampal mitochondria, insulin-induced hypoglycemia increases the respiratory control ratio whereas both situations, hyper- and hypoglycemia, potentiate H2O2 production and decrease the activity of MnSOD. These results suggest that the poor glycemic control that occurs in type 1 diabetic patients undergoing insulin therapy may have detrimental effects in brain areas involved in learning and memory. (C) 2010 Elsevier B.V All rights reserved.
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