title: The influence of diabetes on glutamate metabolism in retinas.
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.
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Gowda
authors.forename: William J
authors.initials: WJ
authors.lastname: Zinnanti
authors.forename: Kathryn F
authors.initials: KF
authors.lastname: LaNoue
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D000637:Transaminases / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D018698:Glutamic Acid; D019289:Pyruvic Acid; D000637:Transaminases; C019798:branched-chain-amino-acid transaminase