||Hiroyuki Kubota, Shinya Kuroda, Temporal coding of insulin signaling, Protein Modifications in Pathogenic Dysregulation of Signaling, 10.1007/978-4-431-55561-2_7, pp.95-109, 2015.09, During recent years, it has become clearer that temporal patterns of stimuli and molecules are important in the regulation of cellular functions. For example, many hormones show distinct temporal patterns in vivo, which are important for homeostasis. One of the unique characteristics of cellular signaling pathways is that a common signaling pathway can selectively regulate multiple cellular functions depending on their temporal patterns. Therefore, one of the major advances in understanding the "pathogenic dysregulation of signaling" is to reveal the temporal coding mechanisms of signaling pathways related to pathogenesis. A systems biological approach combining experiments and computational analysis is necessary to address this issue. In this chapter, we will introduce the concept that the insulin- dependent AKT pathway uses temporal patterns multiplexing for selective regulation of signaling molecules and metabolites, which depend on their network structures and kinetics, using rat hepatoma Fao cells. These results represent a huge step forward in our understanding of insulin actions and type II diabetes mellitus ..