Alterations of Brain Energy Metabolism in Type 2 Diabetic Goto-Kakizaki Rats Measured In Vivo by (13)C Magnetic Resonance Spectroscopy
(2019) In Neurotoxicity Research 36(2). p.268-278- 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.
(Less)
- author
- Girault, Freya-Merret ; Sonnay, Sarah LU ; Gruetter, Rolf and Duarte, João M N LU
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- keywords
- Journal Article
- in
- Neurotoxicity Research
- volume
- 36
- issue
- 2
- pages
- 268 - 278
- publisher
- Springer
- external identifiers
-
- pmid:28971314
- scopus:85030253878
- ISSN
- 1029-8428
- DOI
- 10.1007/s12640-017-9821-y
- language
- English
- LU publication?
- no
- id
- 3afa9672-d027-46c4-af32-2e1a183b5a17
- date added to LUP
- 2017-10-19 15:02:47
- date last changed
- 2025-01-07 22:25:14
@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 < 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.</p>}}, author = {{Girault, Freya-Merret and Sonnay, Sarah and Gruetter, Rolf and Duarte, João M N}}, issn = {{1029-8428}}, keywords = {{Journal Article}}, language = {{eng}}, number = {{2}}, pages = {{268--278}}, publisher = {{Springer}}, 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}}, doi = {{10.1007/s12640-017-9821-y}}, volume = {{36}}, year = {{2019}}, }