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Alteration of Interaction Between Astrocytes and Neurons in Different Stages of Diabetes: a Nuclear Magnetic Resonance Study Using [1-13C]Glucose and [2-13C]Acetate

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Abstract

Increasing evidence has shown that the brain is a site of diabetic end-organ damage. This study investigates cerebral metabolism and the interactions between astrocytes and neurons at different stages of diabetes to identify the potential pathogenesis of diabetic encephalopathy. [1-13C]glucose or [2-13C]acetate is infused into 1- and 15-week diabetic rats, the brain extracts of which are analyzed by using 1H and 13C magnetic resonance spectroscopy. The 13C-labeling pattern and enrichment of cerebral metabolites are also investigated. The increased 13C incorporation in the glutamine, glutamate, and γ-aminobutyric acid carbons from [2-13C]acetate suggests that the astrocytic mitochondrial metabolism is enhanced in 1-week diabetic rats. By contrast, the decreased labeling from [1-13C]glucose reflected that the neuronal mitochondrial metabolism is impaired. As diabetes developed to 15 weeks, glutamine and glutamate concentrations significantly decreased. The increased labeling of glutamine C4 but unchanged labeling of glutamate C4 from [2-13C]acetate suggests decreased astrocyte supply to the neurons. In addition, the enhanced pyruvate recycling pathway manifested by the increased lactate C2 enrichment in 1-week diabetic rats is weakened in 15-week diabetic rats. Our study demonstrates the overall metabolism disturbances, changes in specific metabolic pathways, and interaction between astrocytes and neurons during the onset and development of diabetes. These results contribute to the mechanistic understanding of diabetes pathogenesis and evolution.

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Abbreviations

DM:

Diabetes mellitus

NAA:

N-acetyl aspartate

m-Ins:

Myo-inositol

1H NMR:

Proton nuclear magnetic resonance

Cho:

Choline

LDH:

Lactate dehydrogenase

PDH:

Pyruvate dehydrogenase

PC:

Pyruvate carboxylase

MCA:

Monocarboxylic acid

GS:

Glutamine synthetase

Glu:

Glutamate

Gln:

Glutamine

TCA:

Tricarboxylic acid

ALAT:

Alanine aminotransferase

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Acknowledgments

We thank Huan Zhu and Jian-min Jia for their participation. This work was supported by the National Natural Science Foundation of China (No. 21175099), the Zhejiang Provincial Natural Science Foundation of China (No. LY14H090014), the Zhejiang Provincial Program for the Cultivation of Health talents, and the Science and Technology Foundation of Wenzhou (No. Y20100005).

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Authors and Affiliations

  1. Radiology Department of the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Na Wang, Wei-Jian Chen, Zi-Long Hu & Yun-Jun Yang

  2. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Na Wang, Liang-Cai Zhao, Yong-Quan Zheng, Min-Jian Dong, Zi-Long Hu & Hong-Chang Gao

  3. Department of Chemistry and Francis Bitter Magnet Laboratory, Massachusetts Institute of Technology Cambridge, Cambridge, MA, 02139, USA

    Yongchao Su

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  1. Na Wang
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Correspondence to Yun-Jun Yang or Hong-Chang Gao.

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Wang, N., Zhao, LC., Zheng, YQ. et al. Alteration of Interaction Between Astrocytes and Neurons in Different Stages of Diabetes: a Nuclear Magnetic Resonance Study Using [1-13C]Glucose and [2-13C]Acetate. Mol Neurobiol 51, 843–852 (2015). https://doi.org/10.1007/s12035-014-8808-4

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