Abstract
This chapter reviews the glucose-insulin control system. First, classic control theory is described briefly and compared with biological control. The following analysis of the control system falls into two parts: a glucose-sensing part and a glucose-controlling part. The complex metabolic pathways are divided into smaller pieces and analyzed via several small biosimulation models that describe events in beta cells, liver, muscle and adipose tissue etc. In the glucose-sensing part, the beta cell are shown to have some characteristics of a classic PID controller, but with nonlinear properties. Furthermore, the body has also glucose sensors in the intestine, the brain, the portal vein, and to some extent the liver, and they sense very different glucose concentrations. All sensors are incorporated in a dynamic network that is interconnected by both hormones and the nervous system. Regarding glucose control, the analysis shows that the system has many more facets than just keeping the glucose concentration within narrow limits. After glucose enters the cell and is phosphorylated to glucose-6-phosphate, the handling of glucose-6-phosphate is critical for glucose regulation. Also, this handling is influenced by insulin. Another facet is that the control system has to cope with the complex traffic of metabolites inside cells and between organs on time-scales from minutes to months or more. The analysis is evaluated using setups called "virtual experiments", i.e. biosimulation models describing common experimental scenarios like the fasting state, the fed state, glucose tolerance tests, and glucose clamps. The main finding is that the glucose-insulin control system does not work as an isolated control of the plasma glucose concentration. The system seems more designed to control the different nutrient and metabolic fluxes between storage, release, and oxidation, and between the different organs. In this control, both insulin and the nervous system are instrumental.
| Original language | English |
|---|---|
| Title of host publication | Biosimulation in Drug Development |
| Number of pages | 56 |
| Publisher | Wiley-VCH |
| Publication date | 11 Jul 2008 |
| Pages | 141-196 |
| ISBN (Print) | 9783527316991 |
| DOIs | |
| Publication status | Published - 11 Jul 2008 |
Keywords
- Biosimulation
- Drug metabolism
- Glucose handling
- Glucose sensing
- Glucose-insulin control system
- Simulating cells
- Simulating tissues