Differential effects of type 2 diabetes on brain glycometabolism in rats: focus on glycogen and monocarboxylate transporter 2
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Astrocyte-neuron lactate shuttle (ANLS) is a pathway that supplies glycogen-derived lactate to active neurons via monocarboxylate transporter 2 (MCT2), and is important for maintaining brain functions. Our study revealed alterations of ANLS with hippocampal hyper-glycogen levels and downregulated MCT2 protein levels underlying hippocampal dysfunctions as a complication in type 2 diabetic (T2DM) animals. Since T2DM rats exhibit brain dysfunctions involving several brain regions, we examined whether there might also be T2DM effects on ANLS’s disturbances in other brain loci. OLETF rats exhibited significantly higher glycogen levels in the hippocampus, hypothalamus, and cerebral cortex than did LETO rats. MCT2 protein levels in OLETF rats decreased significantly in the hippocampus and hypothalamus compared to their controls, but a significant correlation with glycogen levels was only observed in the hippocampus. This suggests that the hippocampus may be more vulnerable to T2DM compared to other brain regions in the context of ANLS disruption.
KeywordsAstrocyte-neuron lactate shuttle Brain glycogen Hippocampus Monocarboxylate transporter Type 2 diabetes mellitus
The authors are grateful to Randeep Rakwal, Yu-Fan Liu, Naoki Omori, Katsuhito Saito (University of Tsukuba, Japan) for technical support and discussion, and to Melissa Noguchi (ELCS English Language Consultation, Japan) for help with the manuscript. This study was funded by the “Global Initiative for Sports Neuroscience (GISN): For Development of Exercise Prescription Enhancing Cognitive Functions,” by special funds for Education and Research of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) granted to the “Body and Mind Integrated Sports Sciences (BAMIS) Project” and to the “Human High Performance (HHP) Research Project,” and by the Japan Society for the Promotion of Science (Grants-in-aid for Scientific Research A, No. 15H01828; Challenging Exploratory Research, No. 23650384).
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Conflict of interest
The authors declare that they have no conflict of interest.