Neurotoxicity Research

, Volume 36, Issue 2, pp 268–278 | Cite as

Alterations of Brain Energy Metabolism in Type 2 Diabetic Goto-Kakizaki Rats Measured In Vivo by 13C Magnetic Resonance Spectroscopy

  • Freya-Merret Girault
  • Sarah Sonnay
  • Rolf Gruetter
  • João M. N. DuarteEmail author


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 14.1 T 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.


Insulin resistance Glucose Brain energy metabolism Magnetic resonance spectroscopy Neuron-glia interactions 



Oxidative fraction of CMRglc


Cerebral metabolic rate of glucose


Fractional enrichment


Glucose tolerance test


Apparent Michaelis constant of glucose transport


Magnetic resonance spectroscopy


Type 2 diabetes

TCA cycle

Tricarboxylic acid cycle


Dilution of glial acetyl-CoA


Rate of glial TCA cycle resulting in full pyruvate oxidation


Rate of glutamine synthetase


Dilution of pyruvate


Rate of apparent glutamatergic neurotransmission


Volume of interest


Pyruvate efflux


Rate of pyruvate carboxylase


Glial TCA cycle


Neuronal TCA cycle


Rate of oxoacid-amino acid exchange in glia


Rate of oxoacid-amino acid exchange in neurons


Zucker diabetic fatty



The authors are grateful to Dr. Ana F. Soares (LIFMET, EPFL) for fruitful discussions.


This research was supported by the Swiss National Science Foundation (grant 148250), National Competence Center in Biomedical Imaging (NCCBI), and by Centre d’Imagerie BioMédicale (CIBM) of the UNIL, UNIGE, HUG, CHUV, EPFL, and the Leenaards and Jeantet Foundations.

Compliance with Ethical Standards

All experiments were performed in accordance with the Swiss federal law on animal experimentation and approved by the local authority (EXPANIM-SCAV), and are reported according to the ARRIVE guidelines.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Freya-Merret Girault
    • 1
  • Sarah Sonnay
    • 1
  • Rolf Gruetter
    • 1
    • 2
    • 3
  • João M. N. Duarte
    • 1
    Email author
  1. 1.Laboratory for Functional and Metabolic Imaging (LIFMET), École Polytechnique Fédérale de Lausanne (EPFL)LausanneSwitzerland
  2. 2.Department of RadiologyUniversity of LausanneLausanneSwitzerland
  3. 3.Department of RadiologyUniversity of GenevaGenevaSwitzerland

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