Topp, Promislow, de Vries, Miura, Finegood, 2000

Model Status

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

Model Structure

Diabetes is a disease of the glucose regulatory system that is associated with increased morbidity and premature mortality. There are two main types of diabetes. Type 1 diabetes (also called juvenile onset or insulin-dependent diabetes) is due to an autoimmune attack on the insulin secreting pancreatic beta-cell. Type 2 diabetes (also called adult onset or non-insulin-dependent diabetes) is characterised by a reduced mass of beta-cells, reduced insulin secretion and resistance to the action of insulin (elevated concentrations of glucose in the blood). In healthy individuals, blood glucose levels are controlled by two negative feedback loops. In the short term hyperglycemia (high blood glucose levels) stimulates insulin secretion from the pancreatic beta-cells. This then induces increased glucose uptake and decreased glucose production, leading to a decrease in blood glucose levels. Prolonged hyperglycemia may induce a second negative feedback loop by increasing the rate of beta-cell replication and thus the mass of beta-cells. An increased beta-cell mass represents an increased potential for insulin secretion, which in turn leads to a decrease in blood glucose. Type 2 diabetes has been associated with defects in both the short-term and long-term feedback loops.

The mathematical models produced as part of diabetes research have predominantly concentrated on the dynamics of a single variable, namely blood glucose level, insulin concentration or beta-cell mass. In their 2000 study, Brian Topp, Keith Promislow, Gerda de Vries, Robert M. Miura and Diane T. Finegood combine all three variables in a coupled model of beta-cell mass, insulin and glucose dynamics (see the figure below). They used their model to investigate both the normal behaviour of the glucose regulatory system, and to investigate the effects of defects on the behaviour of the system.

The complete original paper reference is cited below:

A Model of Beta-cell Mass, Insulin, and Glucose Kinetics: Pathways to Diabetes, Brian Topp, Keith Promislow, Gerda de Vries, Robert M. Miura and Diane T. Finegood, 2000, Journal of Theoretical Biology , 206, 605-619. (A PDF version of the article is available for Journal Members on the Journal of Theoretical Biology website.) PubMed ID: 11013117

Schematic diagram of the pancreatic beta-cells. Glucose is taken up and produced in response to insulin secretion and clearance. Beta-cell formation and loss represent the rates at which beta-cells replicate and die.