It has been suggested that increased oxidative stress might be involved in the pathophysiology of diabetic complications. In this study, we investigated the effect of diabetes on the susceptibility of synaptosomes to oxidative stress (induced by the oxidizing pair ascorbate/Fe2+) and on the uptake of the amino acid neurotransmitters γ-aminobutyric acid (GABA) and glutamate. We found a lower susceptibility of synaptosomes isolated from Goto-Kakizaki (GK) rats, a model of non-insulin-dependent diabetes mellitus, to lipid peroxidation as compared with synaptosomes isolated from Wistar control rats (6.40 ± 1.05 and 12.14 ± 1.46 nmol thiobarbituric acid reactive substance/mg protein, respectively). The lower susceptibility of GK rat synaptosomes to membrane lipid peroxidation correlates with an increase in synaptosomal vitamin E levels (835 ± 58.04 and 624.26 ± 50.26 pmol/mg protein in diabetic and normal rats, respectively). In the absence of ascorbate/Fe2+, no significant differences were observed between the levels of lipid peroxidation of synaptosomes isolated from diabetic and normal rats. Studies of neurotransmitter uptake show that the [3H]glutamate uptake was decreased by about 30% in diabetic GK rats as compared with control Wistar rats, whereas the [3H]GABA uptake was not significantly different from controls. Under oxidizing conditions, the glutamate uptake in diabetic rats was unaffected, and a decreased GABA uptake (41.39 ± 4.41 and 60.96 ± 6.4% of control in GK and Wistar rats, respectively) was observed. We conclude that the increased resistance to oxidative stress in GK rat synaptosomes may be due to the increased vitamin E content and that diabetic state and oxidative stress conditions differentially affected the uptake of the neurotransmitters GABA and glutamate.

Keywords:
Stress, Oxidative stress, GABA, Diabetes, Excitatory amino acids, Synaptosomes
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2000
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