A mathematical model of beta-cells in an islet of Langerhans sensing a glucose gradient

作者：Meyer Hermann Michael^*; Benninger Richard K P

来源：HFSP Journal, 2010, 4(2): 61-71.

DOI：10.2976/1.3354862

Pancreatic beta-cells release insulin in response to increased glucose levels. Compared to isolated beta-cells, beta-cells embedded within the islets of Langerhans network exhibit a coordinated and greater insulin secretion response to glucose. This coordinated activity is considered to rely on gap-junctions. We investigated the beta-cell electrophysiology and the calcium dynamics in islets in response to glucose gradients. While at constant glucose the network of beta-cells fires in a correlated fashion, a glucose gradient induces a sharp division into an active and an inactive part. We hypothesized that this sharp transition is mediated by the specific properties of the gap-junctions. We used a mathematical model of the beta-cell electrophysiology in islets to discuss possible origins of this sharp transition in electrical activity. In silico, gap-junctions were required for such a transition. However, the small width of transition was only found when a stochastic variability of the expression of key transmembrane proteins, such as the ATP-dependent potassium channel, was included. The agreement with experimental data was further improved by assuming a delay of gap-junction currents, which points to a role of spatial constraints in the beta-cell. This result clearly demonstrates the power of mathematical modeling in disentangling causal relationships in complex systems. [DOI: 10.2976/1.3354862]

• 出版日期2010-4