January 10, 2011

"Reining" in Diabetes

Interesting article from IEEE Spectrum on the application of control theory to diabetes treatment. This is a good example of rein control (even through they don't name it as such in the article), which is a form of feedforward control broadly applicable to physiological systems. 

The concept of rein control dates to pre-automotive times when a driver would control their team of horses (or some other pack animal) in order to get wagons or other payloads from place to place. The driver would use two reins (or guidewires) that were independently coupled to the team of animals in front. 

Pulling on the reins in different ways would result in a very crude form of steering (controlling direction or speed). The steersman analogy stated in another way!



Rein control in physiology exists when two entities A and B (which could be gene products, paracrine signaling, or hormonal release) act upon the same target. This is fundamentally different from linear feedback, where the action of one entity is reinforced. 

In the IEEE article, the mode of action is different, which contributes to the following: 

 * a compensatory effect when both entities (A and B) act upon the same target. 

* a loss of function when one of the source entities (A or B) fail (as in diabetes, where the beta cells shut down). 

In cases where the number of entities is more than two, we will see much more complex dynamics. In particular, we should see many synthetic (A + B > C) and subadditive effects (A + B < C). 

For more information about applications of control theory to disease and physiological function, please see the following academic references: 

[1] Saunders et.al (1998). Integral Rein Control in Physiology. Journal of Theoretical Biology, 194, 163. 

[2] Saunders, P.T., Koeslag, J.H., and Wessels, J.A. (2000). Integral rein control in physiology II: A general model. Journal of Theoretical Biology, 206(2), 211-220.

[3] Cobelli et.al (2009). Diabetes: models, signals, and control. IEEE Reviews in Biomedical Engineering, 2, 54.

[4] Steersman Analogy: Glanville R. (1997). A ship without a rudder. In: "Problems of excavating cybernetics and systems". R. Glanville and G. de Zeeuw (eds.). BKS+, Southsea, UK.

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