Westermark, Lansner, 2003

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

Understanding stimulus-secretion coupling in pancreatic beta-cells is important for the understanding of glucose homeostasis in diabetes. According to the glucose-mediated stimulus-secretion theory, glucose enters the pancreatic beta-cell via a membrane bound glucose transporter. Once inside the cell it enters the glycolysis pathway where, via several enzyme catalysed steps, it is converted to pyruvate and this then enters the mitochondria. This process increases the ATP to ADP ratio, which in turn causes ATP-sensitive K⁺ channels to close. The resulting membrane depolarisation opens voltage-sensitive Ca²⁺ channels resulting in an increased cytosolic calcium concentration ([Ca²⁺]_i), which in turn is correlated with insulin secretion from secretory vesicles.

The complexity of this system has been described by several mathematical models which have focused on fast bursting in beta-cells. (such as Chay, Extracellular and Intracellular Calcium Effects on Pancreatic Beta Cells, 1997). Slower oscillations, which correlate with insulin secretion, are thought to be due to oscillations in glycolysis. In the study described here, Westermark and Lansner suggest a theoretical model of glycolytic oscillations in the pancreatic beta-cell (see the figure below). Their minimal model couples glucose to the phosphofructokinase (PFK) catalysed reaction. This enzyme is known to cause glycolytic oscillations in yeast and in muscle, and it is also thought to be playing a role in the oscillations in beta-cell glycolysis.

The complete original paper reference is cited below:

A Model of Phosphofructokinase and Glycolytic Oscillations in the Pancreatic Beta-cell, Pal O. Westermark and Anders Lansner, 2003, Biophysical Journal , 85, 126-139. (Full text (HTML) and PDF versions of the article are available to subscribers on the Biophysical Journal website.) PubMed ID: 12829470

Schematic representation of the mathematical model of glycolysis. The fluxes over the enzyme catalysed reactions are denoted v.