Abstract
Type 2 diabetes (T2D) is associated with deterioration of brain structure and function. Here, we tested the hypothesis that T2D induces a reorganization of the brain metabolic networks that support brain function. For that, alterations of neuronal and glial energy metabolism were investigated in a T2D model, the Goto-Kakizaki (GK) rat. 13C magnetic resonance spectroscopy in vivo at 14.1T was used to detect 13C labeling incorporation into carbons of glutamate, glutamine, and aspartate in the brain of GK (n=7) and Wistar (n=13) rats during intravenous [1,6-13C]glucose administration. Labeling of brain glucose and amino acids over time was analyzed with a two-compartment mathematical model of brain energy metabolism to determine the rates of metabolic pathways in neurons and glia. Compared to controls, GK rats displayed lower rates of brain glutamine synthesis (-32%, P<0.001) and glutamate-glutamine cycle (-40%, P<0.001), and mitochondrial tricarboxylic acid (TCA) cycle rate in neurons (-7%, P=0.036). In contrast, the TCA cycle rate of astrocytes was larger in GK rats than controls (+21%, P=0.042). We conclude that T2D alters brain energy metabolism and impairs the glutamate-glutamine cycle between neurons and astrocytes, in line with diabetes-induced neurodegeneration and astrogliosis underlying brain dysfunction.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
