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The influence of diabetes on glutamate metabolism in retinas
Author(s) -
Gowda Kavitha,
Zinnanti William J.,
LaNoue Kathryn F.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07206.x
Subject(s) - glutamate receptor , excitotoxicity , endocrinology , medicine , metabolism , biology , glutamatergic , glutamic acid , biochemistry , diabetes mellitus , chemistry , amino acid , receptor
J. Neurochem. (2011) 117 , 309–320. Abstract Excised retinas from euglycemic and diabetic Sprague–Dawley rats were studied to evaluate differences in glutamate metabolism related to diabetes. Reports suggest, neuronal cell death possibly caused by glutamate excitotoxicity, is an early consequence of diabetes. To monitor the influence of diabetes on glutamate metabolism, we measured glutamatergic neurotransmission, anaplerotic glutamate synthesis from 14 CO 2 and pyruvate as well as rates of glutamate cataplerosis ([U‐ 14 C]glutamate to 14 CO 2 and 14 C‐pyruvate). The data suggest the presence of a glutamate buffering anaplerotic/cataplerotic metabolic cycle in controls which is uncoupled by diabetes. For cycle operation, anaplerosis is initiated by a small pyruvate pool which is also the product of cataplerosis. In the cataplerotic pathway, glutamate conversion to α‐ketoglutarate and then to CO 2 and pyruvate is reduced by 90% in diabetic retinal Müller cells because glutamate transamination by branched chain aminotransferase is competitively inhibited by branched chain amino acids (BCAAs). BCAAs, but not the ketoacids, were almost twice as high in diabetic compared to euglycemic rat retinas. The data suggest the hypothesis that glutamate levels in retinal Müller cells from diabetic rats are elevated because of the presence of excess BCAAs, and that elevated glutamate in Müller cells causes glutamate excitotoxicity.