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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
ORIGINAL ARTICLE

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 14.1 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.

Keywords

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

Abbreviations

CMRglc(ox)

Oxidative fraction of CMRglc

CMRglc

Cerebral metabolic rate of glucose

FE

Fractional enrichment

GTT

Glucose tolerance test

Kt

Apparent Michaelis constant of glucose transport

MRS

Magnetic resonance spectroscopy

T2D

Type 2 diabetes

TCA cycle

Tricarboxylic acid cycle

Vdil

Dilution of glial acetyl-CoA

Vg

Rate of glial TCA cycle resulting in full pyruvate oxidation

VGS

Rate of glutamine synthetase

Vin

Dilution of pyruvate

VNT

Rate of apparent glutamatergic neurotransmission

VOI

Volume of interest

Vout

Pyruvate efflux

VPC

Rate of pyruvate carboxylase

VTCAg

Glial TCA cycle

VTCAn

Neuronal TCA cycle

VXg

Rate of oxoacid-amino acid exchange in glia

VXn

Rate of oxoacid-amino acid exchange in neurons

ZDF

Zucker diabetic fatty

Notes

Acknowledgements

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

Funding

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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