Insulin Receptor Signaling in Normal and Insulin-Resistant States
Insulin Receptor Signaling in Normal and Insulin-Resistant States
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DOI：
10.1101/cshperspect.a009191
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发表时间：
2014-01-01
影响因子：
7.2
通讯作者：
Kahn, C. Ronald
中科院分区：
文献类型：
--
作者：
Boucher, Jeremie;Kleinridders, Andre;Kahn, C. Ronald
随着2型糖尿病在全球范围内的增加，研究的一个主要焦点是了解影响这种疾病的信号通路。胰岛素信号主要通过作用于肝脏、骨骼肌和脂肪组织来调节葡萄糖、脂质和能量稳态。当个体从进食状态转变为禁食状态时，对这一通路的精确调节对于适应至关重要。作用于信号传导途径不同步骤的正性和负性调节剂以及蛋白质同种型相互作用的多样性确保了不同组织中对胰岛素的适当和协调的生物反应。虽然基因突变是罕见和严重的胰岛素抵抗的原因，但肥胖可通过多种机制导致胰岛素抵抗。了解这些途径对于开发治疗糖尿病、代谢综合征及其并发症的新药至关重要。
In the wake of the worldwide increase in type-2 diabetes, a major focus of research is understanding the signaling pathways impacting this disease. Insulin signaling regulates glucose, lipid, and energy homeostasis, predominantly via action on liver, skeletal muscle, and adipose tissue. Precise modulation of this pathway is vital for adaption as the individual moves from the fed to the fasted state. The positive and negative modulators acting on different steps of the signaling pathway, as well as the diversity of protein isoform interaction, ensure a proper and coordinated biological response to insulin in different tissues. Whereas genetic mutations are causes of rare and severe insulin resistance, obesity can lead to insulin resistance through a variety of mechanisms. Understanding these pathways is essential for development of new drugs to treat diabetes, metabolic syndrome, and their complications.