Optimal homeostasis necessitates bistable control.

Bistability is a fundamental phenomenon in nature. In biology, a number of fine properties of bistability have been identified. However, these properties are only consequences of bistability at the physiological level, which do not explain why it had to emerge during evolution. Using optimal homeostasis as the first principle, I find that bistability emerges as an indispensable control mechanism. It is the only solution to a dilemma in glucose homeostasis: high insulin efficiency is required to confer rapidness in plasma glucose clearance, whereas an insulin sparing state is required to guarantee the brain's safety during fasting. The optimality consideration renders a clear correspondence between the molecular and physiological levels. This new perspective can illuminate studies on the twin epidemics of obesity and diabetes and the corresponding intervening strategies. For example, overnutrition and sedentary lifestyle may represent sudden environmental changes that cause the lose of optimality, which may contribute to the marked rise of obesity and diabetes in our generation. Because this bistability result is independent of the parameters of the mathematical model (for which the result is quite general), some other biological systems may also use bistability to control homeostasis.