Role of importin-alpha in the regulation of glucose-responsive gene expression

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Glucose is the preferred nutrient for most animal cells, including man. In order for a cell to adapt to changes in nutrient supply, the availability of glucose has to be sensed and rapidly communicated to the cell's nucleus, which contains the genes arrayed on chromosomes. Once the signal has reached the nucleus, a unique set of genes are transcribed, ultimately leading to the production of proteins that promote proper uptake and metabolism of glucose. This signaling depends on the function of proteins in the nucleus called transcriptional regulators, which ensure proper gene activation. We propose to define at a molecular level the signaling events that connect the detection of extracellular glucose and the activation of glucose-regulated genes, reactions that are not completely understood. We expect that our research will provide new insights into fundamental biological processes, which are crucial to the physiology of cells, organs and organisms under normal and disease conditions, such as diabetes and obesity.