Cooperation between brain and islet in glucose homeostasis and diabetes

摘要

胰岛素及其对葡萄糖平衡的诸多效应的发现， 长期以来决定着我们对糖尿病及其治疗的认识。但我们对大脑的关注却要少得多--除了感觉以及对低血糖做出反应外，大脑传统上被认为在这方面只起一个小作用。这篇Review文章总结新发现的关于存在一个与胰岛共同作用来降低血糖的、以大脑为中心的血糖调控系统的证据。以上两个调控系统以广泛的重叠和冗余为特点，所以二者中的缺陷也许都是罹患糖尿病所必需的。作者的结论是：要更有效地防止糖尿病流行，就应当开发瞄准以大脑及以胰岛为中心的系统的治疗方法。%Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as 'glucose effectiveness', account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not.