A mathematical model of brain glucose homeostasis.
BACKGROUND
The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG) regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation.


METHODS
In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB) adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model.


RESULTS
It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia.


CONCLUSIONS
Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.
Gaohua
Lu
L
Brain Science Institute, the Institute of Physical and Chemical Research (RIKEN) 2271-130 Anagahora, Shimoshidami, Moriyama-ku, Nagoya, 463-0003, Japan. lu@brain.riken.jp
Kimura
Hidenori
H
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D003198:Computer Simulation; D003920:Diabetes Mellitus / Q000473:pathology; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007700:Kinetics; D008962:Models, Theoretical
D007328:Insulin; D005934:Glucagon; D005947:Glucose