Dysregulation of Glycogen Metabolism with Concomitant Spatial Memory Dysfunction in Type 2 Diabetes: Potential Beneficial Effects of Chronic Exercise

Cognitive dysfunction is one of the comorbidities of diabetes mellitus, but hippocampus-dependent learning and memory, a component of cognitive function, shows particular decline in type 2 diabetes, suggesting an increased risk for dementia and Alzheimer’s disease. Cognitive function is related to dysregulated glucose metabolism, which is the typical cause of type 2 diabetes; however, hippocampal glycogen and its metabolite lactate are also crucial for hippocampus-dependent memory function. Type 2 diabetes induced hippocampus-dependent learning and memory dysfunction can be improved by chronic exercise and this improvement may possibly mediate through an adaptation of the astrocyte-neuron lactate shuttle (ANLS). This chapter focuses on the dysregulation of hippocampal glycometabolism in type 2 diabetes examining both existing evidence as well as the potential underlying pathophysiological mechanism responsible for memory dysfunction in type 2 diabetes, and showing for the first time that chronic exercise could be an effective therapy for type-2-diabetes-induced hippocampal memory decline.