Reducing Glut2 throughout the body does not result in cognitive behaviour differences in aged male mice

OBJECTIVES: GLUT2 is a major facilitative glucose transporter, expressed from the SLC2A2 gene, with essential roles in the liver. Recent work in mice has shown that preventing Glut2 production in specific neuronal populations increases sugar-seeking behaviour, highlighting the importance of Slc2a2 gene expression in the brain. It implies that reduced GLUT2 in the brain, due to genetic polymorphisms or disease, impacts health through behaviour change. Defects in glucose transport in the brain are observed in conditions including type-2 diabetes and dementia. Few studies have directly examined the effect of modulating neuronal glucose transporter expression on cognitive function. The aim of this study was to investigate whether inactivating one Slc2a2 allele throughout the body had major effects on cognition. Cognitive tests to assess recognition memory, spatial working memory and anxiety were performed in Slc2a2 whole-body heterozygous mice (i.e. reduced Glut2 mRNA and protein), alongside littermates expressing normal levels of the transporter. RESULTS: No significant effects on neurological functions and cognitive capabilities were observed in mice lacking one Slc2a2 allele when fed a chow diet. This suggests that the minor variations in GLUT2 levels that occur in the human population are unlikely to influence behaviour and basic cognition.