Cortical and hippocampal mitochondria bioenergetics and oxidative status during hyperglycemia and/or insulin-induced hypoglycemia.
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., 50mg/kg body weight] and STZ-treated rats injected with insulin [s.c., dose adjusted to blood glucose levels] 1h 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 (H(2)O(2)) production rate, and non-enzymatic and enzymatic antioxidant defenses. Cortical mitochondria from insulin-induced hypoglycemic rats present a significant decrease in the ADP/O 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 H(2)O(2) 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.
Cardoso
Susana
S
Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
Santos
Maria S
MS
Seiça
Raquel
R
Moreira
Paula I
PI
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D004734:Energy Metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D007328:Insulin; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D001786:Blood Glucose; D005978:Glutathione; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase; D006442:Glycated Hemoglobin; D007328:Insulin; D017382:Reactive Oxygen Species; D013311:Streptozocin; D013482:Superoxide Dismutase; D017392:Thiobarbituric Acid Reactive Substances