caa a22 4500 463254597 CHVBK 20180405153351.0 cr unu---uuuuu 170326e20071201xx s 000 0 eng 10.1007/s10571-007-9198-1 doi (NATIONALLICENCE)springer-10.1007/s10571-007-9198-1 Enhanced [3H] Glutamate Binding in the Cerebellum of Insulin-Induced Hypoglycaemic and Streptozotocin-Induced Diabetic Rats [Elektronische Daten] [Anu Joseph, Remya Robinson, C. Paulose] Aim Energy deprivation causes neuronal death affecting the cognitive and memory ability of an individual. The kinetic parameters of glutamate dehydrogenase (GDH), the enzyme involved in the production of glutamate, was studied in the cerebellum and liver and the binding parameters of glutamate receptors in the cerebellum of insulin-induced hypoglycaemic and streptozotocin-induced diabetic rats were studied to reveal the role of glutamate excitotoxicity. Methods A single intrafemoral dose of streptozotocin was administered to induce diabetes. Hypoglycaemia was induced by appropriate doses of insulin subcutaneously in control and diabetic rats. The kinetic parameters V max and K m of GDH were studied spectrophotometrically at different substrate concentrations of α-ketoglutarate. Glutamate receptor binding assay was done with different concentrations of [3H] Glutamate. Results The GDH enzyme assay showed a significant increase (P<0.001) in the V max of the enzyme in the cerebellum of hypoglycaemic and diabetic rat groups when compared to control. The V max of hypoglycaemic groups was significantly increased (P<0.001) when compared to diabetic group. In the liver, the V max of GDH was significantly increased (P<0.001) in the diabetic and diabetic hypoglycaemia group when compared to control. The V max of GDH increased significantly (P<0.001) in the diabetic hypoglycaemic rats compared to diabetic group, whereas the control hypoglycaemic rats showed a significant decrease in V max (P<0.001) when compared to diabetic and diabetic hypoglycaemic rats. The K m showed no significant change amongst the groups in cerebellum and liver. Scatchard analysis showed a significant increase (P<0.001) in B max in the cerebellum of hypoglycaemic and diabetic rats when compared to control. The B max of hypoglycaemic rats significantly increased (P<0.001) when compared to diabetic group. In hypoglycaemic groups, B max of the control hypoglycaemic rats showed a significant increase (P<0.001) compared to diabetic hypoglycaemic rats. The K d of the diabetic group decreased significantly (P<0.01) when compared to control and control hypoglycaemic rats. There was a significant decrease (P<0.05) in the K d of diabetic hypoglycaemic group when compared to the control hypoglycaemic rats. Conclusion Our studies demonstrated the increased enzyme activity in the hypoglycaemic rats with increased production of extracellular glutamate. The present study also revealed increased binding parameters of glutamate receptors reflecting an increased receptor number with increase in the affinity. This increased number of receptors and the increased glutamate production will lead to glutamate excitotoxicity and neuronal degeneration which has an impact on the cognitive and memory ability. This has immense clinical significance in the management of diabetes and insulin therapy. Springer Science+Business Media, LLC, 2007 Hypoglycaemia nationallicence Diabetes nationallicence Glutamate dehydrogenase nationallicence Glutamate receptors nationallicence Cerebellum nationallicence Liver nationallicence Joseph Anu Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, 682 022, Cochin, Kerala, India aut Robinson Remya Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, 682 022, Cochin, Kerala, India aut Paulose C. Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, 682 022, Cochin, Kerala, India aut Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/8(2007-12-01), 1085-1095 0272-4340 27:8<1085 2007 27 10571 https://doi.org/10.1007/s10571-007-9198-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-007-9198-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Joseph Anu Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, 682 022, Cochin, Kerala, India aut NATIONALLICENCE 700 1- Robinson Remya Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, 682 022, Cochin, Kerala, India aut NATIONALLICENCE 700 1- Paulose C. Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, 682 022, Cochin, Kerala, India aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/8(2007-12-01), 1085-1095 0272-4340 27:8<1085 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer