Department of Physics, George Washington University, Washington, DC 20052, USA.
J R Soc Interface. 2012 Oct 7;9(75):2723-34. doi: 10.1098/rsif.2012.0244. Epub 2012 Apr 25.
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.
双稳性是自然界的基本现象。在生物学中，已经确定了双稳性的许多精细特性。然而，这些特性只是生理水平上双稳性的结果，它们并不能解释为什么在进化过程中必须出现双稳性。我以最优稳态为第一原理，发现双稳性是作为一种不可或缺的控制机制出现的。它是解决葡萄糖稳态两难困境的唯一方法：快速清除血浆葡萄糖需要高胰岛素效率，而在禁食期间需要胰岛素节约状态以保证大脑的安全。优化考虑使分子和生理水平之间产生了清晰的对应关系。这种新视角可以阐明肥胖和糖尿病这两种流行病及其相应干预策略的研究。例如，营养过剩和久坐的生活方式可能代表着环境的突然变化，导致失去最优性，这可能导致肥胖和糖尿病在我们这一代人中明显增加。由于这种双稳性结果不依赖于数学模型的参数（对于该结果，这是相当普遍的），因此其他一些生物系统也可能使用双稳性来控制稳态。
