胰岛素受体 （IR） 是一种II型受体酪氨酸激酶，对代谢、生长和增殖发挥着至关重要的作用。IR信号的失调与许多人类疾病相关，如糖尿病和癌症。冷冻电子显微学的决议革命在最近几年中导致了几个结构的决定，其中包含不同数量的结合胰岛素分子的IR，这极大地提高了我们对IR如何被胰岛素激活的理解。在这里，我们回顾了IR的胰岛素诱导激活机制，包括（a）位点1和位点2处胰岛素的详细结合模式和功能，以及（b）需要IR激活的胰岛素诱导结构转换。我们强调了IR信号激活和调控的其他关键方面，并讨论了我们对IR激活机制的理解中仍存在的空白和未来研究的潜在途径。《生物化学年度评论》第92卷的最终在线发表日期预计为2023年6月。请参见http://www.annualreviews.org/page/journal/pubdates以获取修订后的估计数据。

The insulin receptor (IR) is a type II receptor tyrosine kinase that plays essential roles in metabolism, growth, and proliferation. Dysregulation of IR signaling is linked to many human diseases, such as diabetes and cancers. The resolution revolution in cryo-electron microscopy has led to the determination of several structures of IR with different numbers of bound insulin molecules in recent years, which have tremendously improved our understanding of how IR is activated by insulin. Here, we review the insulin-induced activation mechanism of IR, including (a) the detailed binding modes and functions of insulin at site 1 and site 2 and (b) the insulin-induced structural transitions that are required for IR activation. We highlight several other key aspects of the activation and regulation of IR signaling and discuss the remaining gaps in our understanding of the IR activation mechanism and potential avenues of future research. Expected final online publication date for the Annual Review of Biochemistry, Volume 92 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.