Ionic mechanisms and Ca dynamics underlying the glucose response of pancreatic cells: a simulation study

The pancreatic  cell has a unique function of converting variations in the extracellular glucose concentration ([G]) to electrical activity, thereby controlling the level of insulin secretion. This signal transduction is dependent on the interaction between energy metabolism and membrane excitation. Several mechanisms have been suggested underlying this bilateral coupling in pancreatic  cells. The gating of ATP-sensitive K channels is regulated by fluctuations in the intracellular concentration of ATP or MgADP ([ATP] or [MgADP]), resulting in a prolongation of the duration of the burst of action potentials with increasing [G]. The activation of L-type Ca channels by an increase of [ATP] (Smith et al., 1989), or the depression of Na/K pump (NaK) activity up to 50% by increasing [G] (Owada et al., 1999), may also favor burst prolongation. In addition, variations in intracellular ion concentrations may have varying influences on individual channels or transporters depending on [G]. For example, it has been recently