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Abstract
BackgroundThe 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.MethodsIn 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.ResultsIt 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.ConclusionSimulations 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.
Highlights
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
The physiological fact that maintenance of a constant brain glucose level is more important than that of blood glucose level suggests that the ultimate goal of the GIG regulatory system, which consists of peripheral GIG interactions and central brain-endocrine crosstalk, is homeostasis of glucose concentration in the brain rather than in the blood
The control of brain glucose homeostasis was considered as the ultimate goal of the glucose-insulinglucagon (GIG) regulatory system
Summary
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. The concentration of blood glucose is controlled continuously through regulatory hormones, mainly insulin and glucagon. In addition to peripheral GIG interactions, the recently recognized central brain-endocrine crosstalk plays a critical role in glucose homeostasis [1]. The physiological fact that maintenance of a constant brain glucose level is more important than that of blood glucose level suggests that the ultimate goal of the GIG regulatory system, which consists of peripheral GIG interactions and central brain-endocrine crosstalk, is homeostasis of glucose concentration in the brain rather than in the blood
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