Brain control of blood glucose levels: implications for the pathogenesis of type 2 diabetes.
Brain control of blood glucose levels: implications for the pathogenesis of type 2 diabetes.
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DOI：
10.1007/s00125-020-05293-3
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发表时间：
2021-01
期刊：
影响因子：
8.2
通讯作者：
Schwartz MW
中科院分区：
文献类型：
--
作者：
Alonge KM;D'Alessio DA;Schwartz MW
尽管文献迅速增长，大脑在正常葡萄糖稳态和2型糖尿病发病机制中所起的作用仍然知之甚少。在这篇综述中，我们介绍了一个框架，以了解大脑在这些过程中的重要作用的基础上，证据表明，大脑，如胰腺，配备了感知和响应循环葡萄糖水平的变化。此外，我们审查的证据表明，葡萄糖感知大脑在建立血糖的防御水平发挥着重要作用，在这个控制系统的缺陷有助于2型糖尿病的发病机制。我们还认为肥胖和2型糖尿病之间的密切联系可能是由于高度整合的神经回路控制能量稳态和葡萄糖稳态的共同缺陷。因此，尽管肥胖的特征在于身体的燃料储存（例如脂肪量）的防御水平的增加，2型糖尿病的特征在于身体的可用燃料（例如循环葡萄糖）的防御水平的增加，在每种情况下的潜在发病机制涉及相关体液负反馈信号的感知（或响应）受损。越来越多的临床前证据加强了这一观点，即在2型糖尿病中，通过恢复大脑正确感知循环葡萄糖水平的能力的治疗，血糖的防御水平可以恢复到正常水平。
Despite a rapidly growing literature, the role played by the brain in both normal glucose homeostasis and in type 2 diabetes pathogenesis remains poorly understood. In this review, we introduce a framework for understanding the brain’s essential role in these processes based on evidence that the brain, like the pancreas, is equipped to sense and respond to changes in the circulating glucose level. Further, we review evidence that glucose sensing by the brain plays a fundamental role in establishing the defended level of blood glucose, and that defects in this control system contribute to type 2 diabetes pathogenesis. We also consider the possibility that the close association between obesity and type 2 diabetes arises from a shared defect in the highly integrated neurocircuitry governing energy homeostasis and glucose homeostasis. Thus, whereas obesity is characterised by an increase in the defended level of the body’s fuel stores (e.g. adipose mass), type 2 diabetes is characterised by an increase in the defended level of the body’s available fuel (e.g. circulating glucose), with the underlying pathogenesis in each case involving impaired sensing of (or responsiveness to) relevant humoral negative feedback signals. This perspective is strengthened by growing preclinical evidence that in type 2 diabetes the defended level of blood glucose can be restored to normal by therapies that restore the brain’s ability to properly sense the circulating glucose level.
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