A Model-based Analysis of Glycolytic Oscillations and Electrical Activity in Pancreatic Alpha-cells

Abstract

It is well known that glucagon secretion is essential in blood glucose homeostasis and its defective regulation in diabetes disease has also been established (Lee, et al., 2012). Therefore, it is of key physiological interest to elucidate the underlying mechanisms of stimulus-secretion coupling in α-cells. Glucagon secretion in this cell type is associated with cytosolic Ca2+ increase evoked by firing action potentials at low glucose concentration. However, given the complexity of the network of regulations involved in this process, modelling approaches are required (Watts & Sherman, 2014). Due to evidence of metabolic oscillations in this cell type (Li, et al., 2015), we analyzed the possible contribution of glycolytic oscillations to the characteristic electrical activity in α-cells. To do it, we modified the model proposed by Bertram, et al. (2004) which is capable to reproduce not only glycolytic and electrical oscillations but also compound oscillations in β-cells. Since glycolytic behaviour is expected to be similar in α- and β -cells (Heimberg, et al., 1995), we focused on the differences in electrical activity, specifically in cell capacitance and KATP channels. We found that because of cell capacitance and difference in maximal conductance of KATP channels, α-cells are electrically active at low glucose, in contrast to the situation in β-cells. Besides, the model suggested that the electrical activity of α-cells is insensitive to glycolytic oscillations.