Abstract
This study reports the effects of alloxan induced diabetes on glucose metabolism enzymes viz. Hexokinase, Lactate dehydrogenase, and Glucose-6-phosphate dehydrogenase from discrete brain regions. Enzymes activity was assayed from hypothalamic areas such as medial preoptic area and median eminence-arcuate region which have gonadotropin releasing hormone cell bodies and their terminals, respectively and other brain regions like septum, amygdala, hippocampus, and thalamus. In all the areas studied, induction of diabetes resulted in a significant decrease in particulate bound HK activity, whereas soluble HK, LDH and G6PDH activity showed increase at 3, 8, 15 and 28 days intervals. Insulin treatment of diabetic rats led to recovery in enzyme activity. Blood glucose levels increased significantly after induction of diabetes and recovery was seen after insulin treatment. The present results suggest that altered cerebral glucose metabolism may also be responsible for reproductive failure observed in diabetic rats. (Mol Cell Biochem141: 97–102, 1994)
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Bestetti G, Locatelli V, Tirone F, Rossi GL, Muller EE: One month of streptozotocin-diabetes induces different neuroendocrine and morphological alterations in the hypothalamopituitary axis of male and femal rats. Endocrinology 117: 208–216, 1985
Dong Q, Lazarus RM, Wing LS, Vellios M, Handelsman DJ: Pulsatile LH secretion in streptozotocin-induced diabetes in the rat. J Endocrinol 131: 49–56, 1991
Berger J, Biswas C, Vicario P, Strout HV: Decreased expression of the insulin responsive glucose transporter in diabetes and fasting. Nature 340: 70–72, 1989
Mick GJ, Tousey K, McCormick KL: Diminishedin situ glucose-6-phosphate flux in permeabilized adepocytes from striptozotocin-induced diabetic rats. Diabetes 40: 1517–1524, 1991
Sokoloff L: Relation between physiological function and energy metabolism in the central nervous system. J Neurochem 29: 13–26, 1977
Choi TB, Boado RJ, Pardridge WM: Blood brain barrier glucose transporter mRNA is increased in experimental diabetes mellitus. Biochem Biophys Res Commun 164: 375–380, 1989
Mooradian AD, Morin AM: Brain uptake of glucose in diabetes mellitus: The role of glucose transporters. Am J Med Sci 301: 173–177, 1991
Pardridge WM, Triguero D, Farrel CR: Down regulation of blood brain barrier glucose transporter in experimental diabetes. Diabetes 39: 1040–1044, 1990
Schwartz WJ, Gainer H: Suprachiasmatic nucleus: Use of14C-labelled deoxyglucose uptake as a functional marker. Science 197: 1089–1091, 1977
Allen TO, Adler NT, Greenberg JH, Reivich M: Vaginocervical stimulation selectively increases metabolic activity in the rat brain. Science 211: 1070–1072, 1981
Sokoloff L: Measurement of local glucose utilization and its use in localisation of functional activity in the central nervous system of animals and man. Rec Prog Hor Res 39: 75–121, 1983
Asatoor AM, King EJ: Simplified calorimetric blood: sugar method. Biochem J 56:(X/IV), 1954.
Garris DR: Depressed progesterone accumulation by the brain and peripheral tissues of diabetic C57BL/KsJ mice: Normalization by estrogen therapy. Horm Res 25: 37–48, 1987
Sharma C, Manjeshwar R, Weinhouse S: Effects of diet and insulin in glucose adenosine triphosphate phosphotransferases of rat liver. J Biol Chem 238: 3840–3845, 1963
Gumaa K, KcLean P: The kinetic quantitation of ATP D-glucose-6-phosphotransferase. FEBS Lett 27: 293–297, 1972
Bergmeyer HU, Bernt E: Lactate dehydrogenase. In: H. U. Bergmeyer (ed.). Methods in Enzymatic Analysis. Academic Press, New York Vol 2, 1974, pp 574–578
Baquer NZ, McLean P: Evidence for the existence and functional activity of the pentose phosphate pathway in the large particle fraction isolated from rat tissues. Biochem Biophys Res Commun 46: 167–174, 1972
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein estimation with folin-phenol reagent. J Biol Chem 193: 265–275, 1951
Rerup CC: Drug producing diabetes through the damage of the insulin producing cells. Phamacol Rev 22: 485–518, 1970
Di Giulio AM, Tenconi B, La Croix R, Mantegazza P, Abbracchio MP, Cattabeni F, Gorio A: Denervation and hyperinnervation in the nervous system of diabetic animals. II. Monoaminergic and peptidergic alterations in the diabetic encephalopathy. J Neurosci Res 24: 362–368, 1989
Rowland NE, Bellush LL: Diabetes mellitus: Stress, neurochemistry and Biobehaviour. Neurosci Biobehav Rev 13: 199–206, 1989
McCall AL: The impact of diabetes on the CNS. Diabetes 41: 557–570, 1992
Walsh CH, Malins JM: Menstruation and control of diabetes. Br Med J 2: 177, 1977
Adashi EY, Hsueh AJW, Yen SSC: Insulin enhancement of luteinizing hormone and follicle stimulating hormone release by pituitary cells. Endocrinology 108: 1441–1448, 1981
Diamond MP, Wentz AC, Cherrington AD: Alterations in carbohydrate metabolism as they apply to reproductive endocrinology. Fert Ster 50: 387–397, 1988
Van Houten M, Posner BI, Kopriwa BM, Brawer JR: Insulin binding sites localized to nerve terminals in rat median eminence and arcuate nucleus. Science 207: 1081–1083, 1980
Bestetti G, Hofer R, Rossi GL: The preoptic-suprachiasmatic nuclei though morphologically heterogeneous are equally affected by streptozotocin diabetes. Exp Brain Res 66: 74–82, 1987
Copley M, Fromm HJ: Kinetics studies of the brain hexokinase reaction. A reinvestigation with the solubilized brain enzymes. Biochemistry 6: 3503–3509, 1967
Wilson JE: Brain hexokinase, the prototype ambiquotous enzyme. In: B.L. Horecker and E.R. Stadtman (eds). Current topics in cell regulation. Vol 16, Academic Press, New York, 1980, pp 1–53
Solheim LP, Fromm HJ: Kinetic evidence that the high-affinity glucose-6-phosphate site on hexokinase I is the active site. Arch Biochem Biophys 211: 92–99, 1981
Mans AM, De Joseph MR, Davis DW, Hawkins RA: Brain energy metabolism in streptozotocin-diabetes. Biochem J 249: 57–62, 1988
Blackshear PJ, Alberty KGMM: Experimental diabetic ketoacidosis. Sequential changes of metabolic intermediates in blood, liver, cerebrospinal fluid and brain after acute insulin deprivation in the streptozotocindiabetic rat. Biochem J 138: 107–117, 1974
Thurston JH, Hauhart RE, Jones EM, Ater JL: Effects of alloxan diabetes, anti insulin serum diabetes and non-diabetes dehydration in brain and energy metabolism in young mice. J Biol Chem 250: 1751–1758, 1975
Mooradian AD: Diabetic complications of the central nervous system. Endocrinol Rev 9: 346–356, 1988
Krukoff TL, Patel KP: Alterations in brain hexokinase activity associated with streptozotocin-induced diabetes mellitus in the rat. Brain Res 522: 157–160, 1988
Grill V, Gutnaik M, Bjorkman O, Lindovist S, Stone-Elander S, Seitz RT, Blomqvist G, Reichard P, Widen L: Cerebral blood flow and substrate utilization in insulin-treated diabetic subjects. Am J Physiol 258: E813-E820, 1990
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Lakhman, S.S., Sharma, P., Kaur, G. et al. Changes in glucose metabolism from discrete regions of rat brain and its relationship to reproductive failure during experimental diabetes. Mol Cell Biochem 141, 97–102 (1994). https://doi.org/10.1007/BF00926172
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DOI: https://doi.org/10.1007/BF00926172