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Neurochemical Correlates of Alloxan Diabetes: Glucose and Related Brain Metabolism in the Rat

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Abstract

Diabetes mellitus is known to impair glucose metabolism. The fundamental mechanism underlying hyperglycaemia in diabetes mellitus involves decreased utilization of glucose by the brain. However, mechanisms responsible for progressive failure of glycaemic regulation in type I (IDDM) diabetes need extensive and proper understanding. Hence the present study was initiated. Type I diabetes was induced in albino rat models with alloxan monohydrate (40 mg/Kg iv). Cerebral cortex and medulla oblongata were studied 48 h after alloxanisation. Diabetes caused an elevation in glucose, glutamate, aspartate, GABA and taurine levels and a decline in the glutamine synthetase activity. The activities of brain lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) exhibited significant decrease during diabetes. Ammonia content increased (P < 0.01) as a function of diabetes. Na+-K+ ATPase showed an elevation (P < 0.01) and Ca++-ATPase activity decreased (P < 0.01). Calcium content enhanced (P < 0.05) in the brain of diabetic rats. A General increase in the brain AMP, ADP and ATP was found on inducing diabetes. Impaired cerebral glucose metabolism accounts for the failure of cerebral glucose homeostasis. The impairment in the glycaemic control leads to disturbances in cerebral glutamate content (resulting in calcium overload and excitotoxic injury) and brain energy metabolism as reflected by alterations occurring in adenine nucleotide and the ATPases. The failure in the maintenance of normal energy metabolism during diabetes might affect glucose homeostasis leading to gross cerebral dysfunction during diabetes.

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Acknowledgments

Financial assistance provided to Dr. Nayeemunnisa for the research project by the University Grants Commission, India is gratefully acknowledged. The authors are thankful to Prof. B.G. Shivananda for encouragement.

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Correspondence to Nayeemunnisa Ahmed.

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Ahmed, N., Zahra, N. Neurochemical Correlates of Alloxan Diabetes: Glucose and Related Brain Metabolism in the Rat. Neurochem Res 36, 494–505 (2011). https://doi.org/10.1007/s11064-010-0369-y

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