Abstract
Type 2 diabetes mellitus (T2DM) is a risk factor for the development of Alzheimer's disease, and changes in brain energy metabolism have been suggested as a causative mechanism. The aim of this study was to investigate the cerebral metabolism of the important amino acids glutamate and glutamine in the db/db mouse model of T2DM. Glutamate and glutamine are both substrates for mitochondrial oxidation, and oxygen consumption was assessed in isolated brain mitochondria by Seahorse XFe96 analysis. In addition, acutely isolated cerebral cortical and hippocampal slices were incubated with [U-13C]glutamate and [U-13C]glutamine, and tissue extracts were analyzed by gas chromatography-mass spectrometry. The oxygen consumption rate using glutamate and glutamine as substrates was not different in isolated cerebral mitochondria of db/db mice compared to controls. Hippocampal slices of db/db mice exhibited significantly reduced 13C labeling in glutamate, glutamine, GABA, citrate, and aspartate from metabolism of [U-13C]glutamate. Additionally, reduced 13C labeling were observed in GABA, citrate, and aspartate from [U-13C]glutamine metabolism in hippocampal slices of db/db mice when compared to controls. None of these changes were observed in cerebral cortical slices. The results suggest specific hippocampal impairments in glutamate and glutamine metabolism, without affecting mitochondrial oxidation of these substrates, in the db/db mouse.
Highlights
Type 2 diabetes mellitus (T2DM) is a multifaceted metabolic disease characterized by an augmented level of blood glucose caused by insulin resistance
To investigate if the cerebral mitochondrial oxidation of glutamate and glutamine was altered in the db/db mice, oxygen consumption rates (OCRs) of isolated whole-brain mitochondria were assessed with glutamate and glutamine as substrates, both in the presence of malate
We show no significant changes in oxygen consumption of brain mitochondria from db/db mice when provided with glutamate and glutamine, suggesting little or no change in cerebral mitochondrial oxidation of these substrates
Summary
Type 2 diabetes mellitus (T2DM) is a multifaceted metabolic disease characterized by an augmented level of blood glucose caused by insulin resistance. Insulin resistance has been associated with reductions in cerebral glucose utilization, a clinical hallmark of AD [5, 6]. This observation suggests that altered brain energy metabolism might be an accelerating factor in the development of AD in T2DM. Glutamine must be converted into glutamate prior to oxidation Both neurons and astrocytes are able to metabolize glutamate and Neural Plasticity glutamine [12,13,14]. It has recently been shown that oxidation of glutamate through GDH is important for cerebral energy homeostasis [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
