A brain-oriented compartmental model of glucose-insulin-glucagon regulatory system

Abstract

In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in the diabetes, we develop a mathematical model of glucose-insulin-glucagon (GIG) regulatory system consisting of the peripheral GIG interaction and the central brain-endocrine crosstalk. Firstly, the body is approximated compartmentally. Then, the peripheral interactions among the glucose dynamics, insulin dynamics and glucagon dynamics are described mathematically, together with a feedback control loop describing the central brain-endocrine crosstalk for the control of brain glucose homeostasis. Furthermore, the effects of longterm severe stress and the effects of blood-brain barrier (BBB) adaptation to dysglycemia are taken into consideration. The model is validated by comparing model simulation profiles with clinical data concerning the GIG regulatory responses to bolus, durational and continuous glucose infusion. On account of the simulation results of the effects of long-term severe stress and BBB adaptation on the generation of blood hyperglycemia, it is proposed that blood hyperglycemia in the diabetes is an outcome of the control of brain glucose homeostasis.