Integral rein control in physiology

We propose that blood glucose is regulated by a principle which we call integral rein control, in which under most conditions both glucagon and insulin are produced and control is achieved by altering the balance between the two. Like other integral control systems, the mechanism achieves zero steady-state error, which explains how the blood glucose level can remain very nearly constant over a wide range of input and demand. In addition, the use of two hormones makes the system stable against relatively large perturbations in either direction. An important feature of the model is that the set point is not fixed by an external reference but arises out of the dynamics, in particular out of the relation between the rates of production of the two hormones. The model therefore predicts that the consequence of an inability to produce insulin will be not just that the control will be less effective but that the set point will be shifted. This allows us to explain why patients with untreated Type I diabetes mellitus have high blood glucose levels even under conditions of low glucose input, and why it is difficult to maintain the normal level of 5 mmol/1 in patients who are being treated with insulin. It also explains why Type II diabetes is easier to treat.