Mathematical modeling of the glucose–insulin feedback system is necessary to the understanding of the
homeostatic control, to analyze experimental data, to identify and quantify relevant biophysical parameters, to design clinical trials and to evaluate diabetes prevention or disease modification therapies. Much work has been made over the last 30 years, and the time now seems ripe to provide a omprehensive
review. The one here proposed is focused on the most important clinical/experimental tests performed
to understand the mechanism of glucose homeostasis. The review proceeds from models of pancreatic
insulin production, with a oarser/finer level of detail ranging over cellular and subcellular scales, to
short-term organ/tissue models accounting for the intra-venous and the oral glucose tolerance tests as
well as for the euglycemic hyperinsulinemic clamp, to total-body, long-term diabetes models aiming to represent disease progression in terms of b-cell population dynamics over a long period of years.