Oxidative stress affects synaptosomal gamma-aminobutyric acid and glutamate transport in diabetic rats: the role of insulin.
Evidence suggests that oxidative stress is involved in the pathophysiology of diabetic complications and that insulin has a neuroprotective role in oxidative stress conditions. In this study, we evaluated the in vitro effect of insulin in the susceptibility to oxidative stress and in the transport of the amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glutamate in a synaptosomal fraction isolated from male type 2 diabetic Goto-Kakizaki (GK) rat brain cortex. The ascorbate/Fe(2+)-induced increase in thiobarbituric acid reactive substances (TBARSs) was similar in Wistar and GK rats and was not reverted by insulin (1 micromol/l), suggesting that other mechanisms, rather than a direct effect in membrane lipid peroxidation, may mediate insulin neuroprotection. Diabetes did not affect GABA and glutamate transport, despite the significant decrease in membrane potential and ATP/ADP ratio, and insulin increased the uptake of both GABA and glutamate in GK rats. Upon oxidation, there was a decrease in the uptake of both neurotransmitters and an increase in extrasynaptosomal glutamate levels and in ATP/ADP ratio in GK rats. Insulin treatment reverted the ascorbate/Fe(2+)-induced decrease in GABA accumulation, with a decrease in extrasynaptosomal GABA. These results suggest that insulin modulates synaptosomal GABA and/or glutamate transport, thus having a neuroprotective role under oxidizing and/or diabetic conditions.
Center for Neuroscience of Coimbra, University of Coimbra, Coimbra, Portugal.
Ana I
AI
Duarte
Maria S
MS
Santos
Raquel
R
Seiça
Catarina R
CR
Oliveira
D000818:Animals; D001692:Biological Transport; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D015227:Lipid Peroxidation; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007328:Insulin; D017392:Thiobarbituric Acid Reactive Substances; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid