1 Integrative modeling of the pancreatic β-cell Arthur Sherman Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD USA Richard Bertram Department of Mathematics, Florida State University, Tallahassee, FL USA Published in: Wiley Interscience Encyclopedia of Genetics, Genomics, Proteomics, and Bioinformatics, Part 3 Proteomics, M. Dunn, ed., Section 3.8 Systems Biology, R. L. Winslow, ed., John Wiley & Sons, Ltd. DOI: 10.1002/047001153X.g308213 Keywords: insulin, diabetes, glucose, calcium, ion channels, endoplasmic reticulum, ATP, mitochondria, metabolism, acetylcholine, IP3 Abstract: Pancreatic β-cells secrete insulin, which regulates the concentration of plasma glucose. Dysfunction of this system is a necessary contributing factor to Type II diabetes, and may be sufficient. Insulin secretion is controlled by oscillations of membrane potential, called bursting oscillations, which drive oscillations of cytosolic calcium. We describe the development of mathematical models for this mechanism, beginning with the Chay- Keizer model. Introduction Mammalian metabolism is well-adapted to switch between carbohydrate and lipid fuels depending on availability. One of the key hormones involved is insulin, which promotes glucose oxidation and fat storage when carbohydrate is abundant. In the developed world, unprecedented affluence has resulted in chronic excess of both nutrients relative to energy expenditure requirements, leading to an epidemic of obesity,