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

Girault, Freya-Merret; Sonnay, Sarah LU ; Gruetter, Rolf and Duarte, João M N LU (2017) In Neurotoxicity Research
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. (13)C magnetic resonance spectroscopy in vivo at 14.1 T was used to detect (13)C 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-(13)C]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... (More)

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. (13)C magnetic resonance spectroscopy in vivo at 14.1 T was used to detect (13)C 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-(13)C]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.

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author
publishing date
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publication status
epub
keywords
Journal Article
in
Neurotoxicity Research
publisher
Springer New York
external identifiers
  • scopus:85030253878
ISSN
1029-8428
DOI
10.1007/s12640-017-9821-y
language
English
LU publication?
no
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3afa9672-d027-46c4-af32-2e1a183b5a17
date added to LUP
2017-10-19 15:02:47
date last changed
2018-01-07 12:23:00
@article{3afa9672-d027-46c4-af32-2e1a183b5a17,
  abstract     = {<p>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. (13)C magnetic resonance spectroscopy in vivo at 14.1 T was used to detect (13)C 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-(13)C]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 &lt; 0.001) and glutamate-glutamine cycle (- 40%, P &lt; 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.</p>},
  author       = {Girault, Freya-Merret and Sonnay, Sarah and Gruetter, Rolf and Duarte, João M N},
  issn         = {1029-8428},
  keyword      = {Journal Article},
  language     = {eng},
  month        = {10},
  publisher    = {Springer New York},
  series       = {Neurotoxicity Research},
  title        = {Alterations of Brain Energy Metabolism in Type 2 Diabetic Goto-Kakizaki Rats Measured In Vivo by (13)C Magnetic Resonance Spectroscopy},
  url          = {http://dx.doi.org/10.1007/s12640-017-9821-y},
  year         = {2017},
}