Biddinger Sudha B, Kahn C Ronald
Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Annu Rev Physiol. 2006;68:123-58. doi: 10.1146/annurev.physiol.68.040104.124723.
The insulin resistance syndrome refers to a constellation of findings, including glucose intolerance, obesity, dyslipidemia, and hypertension, that promote the development of type 2 diabetes, cardiovascular disease, cancer, and other disorders. Defining the pathophysiological links between insulin resistance, the insulin resistance syndrome, and its sequelae is critical to understanding and treating these disorders. Over the past decade, two approaches have provided important insights into how changes in insulin signaling produce the spectrum of phenotypes associated with insulin resistance. First, studies using tissue-specific knockouts or tissue-specific reconstitution of the insulin receptor in vivo in mice have enabled us to deconstruct the insulin resistance syndromes by dissecting the contributions of different tissues to the insulin-resistant state. Second, in vivo and in vitro studies of the complex network of insulin signaling have provided insight into how insulin resistance can develop in some pathways whereas insulin sensitivity is maintained in others. These data, taken together, give us a framework for understanding the relationship between insulin resistance and the insulin resistance syndromes.
胰岛素抵抗综合征指的是一系列表现，包括葡萄糖不耐受、肥胖、血脂异常和高血压，这些表现会促进2型糖尿病、心血管疾病、癌症及其他疾病的发生发展。明确胰岛素抵抗、胰岛素抵抗综合征及其后遗症之间的病理生理联系对于理解和治疗这些疾病至关重要。在过去十年中，有两种方法为理解胰岛素信号变化如何产生与胰岛素抵抗相关的一系列表型提供了重要见解。首先，在小鼠体内使用组织特异性敲除或胰岛素受体组织特异性重构的研究，使我们能够通过剖析不同组织对胰岛素抵抗状态的贡献来解构胰岛素抵抗综合征。其次，对胰岛素信号复杂网络的体内和体外研究，为理解胰岛素抵抗如何在某些途径中发展而在其他途径中保持胰岛素敏感性提供了见解。综合这些数据，为我们理解胰岛素抵抗与胰岛素抵抗综合征之间的关系提供了一个框架。
