Using what is accessible to measure that which is not: necessity of model of system

Understanding the in vivo functioning of endocrine-metabolic systems requires the quantitative knowledge of system parameters like production/utilization of substrales, secretion/degradation of hormones, and substrate-hormone signaling. Unfortunately, these system parameters are not directly accessible and an indirect measurement approach is needed based on a model of the system. We review first the principals of the model of system methodology focusing on compartmental and input-output modeling. Then, the model of system methodology is applied to the measurement of nonaccessible parameters/variables of the glucose system like glucose fluxes, insulin fluxes, and glucose-insulin signaling.