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

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-[superscript 13]C]glucose or [2-[superscript 13]C]acetate is infused into 1- and 15-week diabetic rats, the brain extracts of which are analyzed by using [superscript 1]H and [superscript 13]C magnetic resonance spectroscopy. The [superscript 13]C-labeling pattern and enrichment of cerebral metabolites are also investigated. The increased [superscript 13]C incorporation in the glutamine, glutamate, and γ-aminobutyric acid carbons from [2-[supercript 13]C]acetate suggests that the astrocytic mitochondrial metabolism is enhanced in 1-week diabetic rats. By contrast, the decreased labeling from [1-[superscript 13]C]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-[superscript 13]C]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.