Loss of Sugar Detection by GLUT2 Affects Glucose Homeostasis in Mice

摘要: Background Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from metabolism. Here, we studied detection extracellular concentrations in vivo by invalidating transduction pathway downstream transporter-detector GLUT2 measured physiological impact this pathway. Methodology/Principal Findings We produced mice that ubiquitously express largest cytoplasmic loop GLUT2, blocking glucose-mediated gene expression vitro without affecting Impairment GLUT2-mediated transiently protected transgenic against starvation streptozotocin-induced diabetes, suggesting both low- high-glucose were not detected. Transgenic favored lipid oxidation, oral was slowly cleared blood due low insulin production, despite massive urinary excretion. Kidney adaptation characterized a lower rate reabsorption, whereas pancreatic associated with larger number small islets. Conclusions/Significance Molecular invalidation GLUT2-loop changed multiple aspects homeostasis, highlighting top-down approach, role membrane receptors as potential therapeutic targets.