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Differential effects of insulin induced hypoglycaemia upon redox balance in distinct rat brain areas

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Abstract

Insulin induced hypoglycaemia does not generate uniform injuries throughout the brain. We hypothesized that redox balance in different brain regions might respond diversely to hypoglycaemia and aimed to test it in the rat brain model. Blood glucose level, malondialdehyde (MDA), protein carbonyl (PC) adducts and superoxide dismutase (Cu2+-Zn2+- SOD) activity in tissue homogenates of the cortex, cerebellum, basal ganglia and brain stem of rat brain (n = 12) were assayed 2 h after intraperitoneal administration of insulin in subcomatous dosage (6.0 IU/Kg diluted in normal saline) against matched controls (n = 8) that received the vehicle only (10 ml/kg). The cortex, cerebellum, basal ganglia and brain stem areas showed significantly higher mean values for MDA and PC products with lower mean Cu2+-Zn2+-SOD activity in the insulin administered hypoglycaemic rats (p < 0.001). Blood glucose level prevailed to be the chief predictor for the intracellular antioxidant status in all areas of the rat brain as evident from the multiple linear regression study. Post hoc ANOVA confirmed that oxidative stress markers were highest in the basal ganglia region compared to other brain areas (p < 0.001 for both MDA and PC products). Results indicated that hypoglycaemia induced impairment in redox balance were most damaging in the basal ganglia and least in the brain stem and cerebellum. We propose that similar mechanisms may contribute to distinctive neurological complications due to hypoglycaemia in human beings after receiving toxic dosage of insulin or intensive insulin therapy for a substantial period.

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Dasgupta, A., Pal, M., Ghosh, T. et al. Differential effects of insulin induced hypoglycaemia upon redox balance in distinct rat brain areas. Orient Pharm Exp Med 13, 279–287 (2013). https://doi.org/10.1007/s13596-013-0111-9

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