Role of glial metabolism in diabetic encephalopathy as detected by high resolution 13C NMR.
The roles of glial energetics and of the glutamine cycle in diabetic encephalopathy have been investigated ex vivo by (13)C NMR in extracts of adult rat brain. Streptozotocin-induced diabetic or euglycemic animals received intravenous infusions of (1-(13)C) glucose in the absence and presence of trifluoroacetic acid or methionine sulfoximine, two selective inhibitors of the glial tricarboxylic acid cycle or of glutamine synthase, respectively. (1-(13)C) glucose infusions resulted in smaller (13)C incorporation in all carbons of cerebral glutamate, glutamine and GABA in the diabetic animals. Co-infusion of trifluoroacetic acid with (1-(13)C) glucose further reduced the (13)C enrichments in cerebral glutamate and glutamine, the decrease being larger in the diabetic animals than in the corresponding euglycemic controls. Methionine sulfoximine decreased to undetectable levels the fractional (13)C enrichment in the carbons of cerebral glutamine in both groups and had no significant effect on (13)C incorporation in glutamate and GABA, suggesting that glutamine is not the main precursor of glutamate and GABA. Additional animals were infused with (1,2-(13)C(2)) acetate, a major substrate of glial metabolism. In this case, (1,2-(13)C(2)) acetate infusions resulted in increased (13)C incorporation in all carbons of glutamate, glutamine and GABA in the diabetic animals. Together, these results reveal that diabetic encephalopathy has an important effect in astroglial metabolism, decreasing glucose transport and metabolism and increasing the relative contribution of glial oxidative metabolism to the support of glutamatergic and GABAergic neurotransmissions.
García-Espinosa
María A
MA
Department of Biochemistry, Hanes Building, Medical Center Blvd, Wake Forest University Medical School, Winston-Salem, NC 27157, USA.
García-Martín
María L
ML
Cerdán
Sebastián
S
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002247:Carbon Isotopes; D018377:Neurotransmitter Agents; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D013311:Streptozocin; D005947:Glucose