A model for glucose control of insulin secretion during 24 h of free living

The aim of this work was to develop a mathematical model describing the fun ctional dependence of insulin secretion on plasma glucose concentrations du ring 24 h of free living. We obtained hourly central venous blood samples f rom a group of healthy volunteers who spent 24 h in a calorimetric chamber, where they consumed standardized meals. Insulin secretory rates were recon structed from plasma C-peptide concentrations by deconvolution. The relatio nship between insulin release and plasma glucose concentrations was modeled as the sum of three components: a static component (describing the depende nce on plasma glucose concentration itself, with an embedded circadian osci llation), a dynamic component (modeling the dependence on glucose rate of c hange), and a residual component (including the fraction of insulin secreti on not explained by glucose levels). The model fit of the individual 24-h s ecretion profiles was satisfactory (within the assigned experimental error of glucose and C-peptide concentrations). The static component yielded a do se-response function in which. insulin release increased quasi-linearly (fr om 40 to 400 pmol/min on average) over the range of 4-9 mmol/l glucose. The dynamic component was significantly different from zero in coincidence wit h meal-related glucose excursions. The circadian oscillation and the residu al component accounted for the day/night difference in the ability of gluco se to stimulate insulin release. Over 24 h, total insulin release averaged 257 +/- 58 nmol (or 43 +/- 10 ii). The static and dynamic component togethe r accounted for similar to 80% of total insulin release. The model proposed here provides a detailed robust description of glucose-related insulin rel ease during free-living conditions. In nondiabetic subjects, non-glucose-de pendent insulin release is a small fraction of total insulin secretion.