Contributions of modeling to understanding stimulus-secretion coupling in pancreatic beta-cells

Mechanisms of ionic control of insulin secretion in beta-cells of the pancreatic islets of Langerhans are reviewed. The focus is on aspects that have been treated by mathematical models, especially those related to bursting electrical activity. The study of these mechanisms is difficult because of the need to consider ionic fluxes, calcium handling, metabolism, and electrical coupling with other cells in the islet. The data come either from islets, where experimental maneuvers tend to have multiple effects, or from isolated cells, which have degraded electrical activity and secretory sensitivity. Modeling aids in the process by integrating data on individual components such as channels and calcium handling and testing hypotheses for coherence and quantitative plausibility. The study of a variety of models has led to some general mathematical results that have yielded qualitative model-independent insights.