A computational study of pancreatic beta cell dynamics in the progression to diabetes

Abstract

Complex interactions within the pancreatic β-cell are responsible for the range of phenomena observed in the progression to type 2 diabetes. Much is now known about the biophysics of this progression, but more remains to be elucidated through experimental and theoretical collaborations. Recent experimental results identify changes in oscillation magnitude and frequency for fluorescent measures of Ca2+ from isolated pancreatic islets over the progression of diabetes in leptin-receptor deficient mice, and in response to varying levels of glucose stimulation. This paper is a computational study of a subset of those results, using adaptations from classic whole cell models for the role of intracellular calcium and ATP/ADP levels in the regulation of membrane potential and insulin secretion for pancreatic β-cells.While the data was collected from probes within a pancreatic islet, the whole-cell models used for simulations represent a single β-cell. Within the Islets of Langerhans, these cells synchronize electrically, and disrupting cell-cell communication may cause disruptions in insulin secretion. Simulations qualitatively recover the data, observe the behavior of inter-dependent variables not reported in the data, and interpret the implications for parameter values required to obtain these results, constrained by the data. Results reproduce frequency and proportional changes in magnitude for Ca2+ traces from both non-diabetic heterozygous controls and new onset diabetic mice at a fixed age and level of glucose.