Tengholm Anders, Idevall-Hagren Olof
Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Uppsala, Sweden.
Vitam Horm. 2009;80:287-311. doi: 10.1016/S0083-6729(08)00611-0.
Many effects of insulin, insulin-like growth factors and other receptor stimuli are mediated via the phospholipid second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP(3)). PIP(3) is formed by the activity of phosphoinositide 3-kinases in the plasma membrane, where it serves to recruit signalling proteins. These proteins coordinate complex events leading to changes in cell metabolism, growth, movement and survival. Over the past decade, new techniques for measurements of PIP(3) in the plasma membrane of individual living cells have markedly improved our understanding of the role of this messenger in a variety of cellular processes. This review summarises the mechanisms involved in formation and degradation of PIP(3) in insulin-responsive cells, how PIP(3) can be measured in individual cells as well as accumulating evidence that the plasma membrane PIP(3) concentration undergoes complex spatio-temporal patterns in many types of cells, with particular emphasis on autocrine insulin-induced PIP(3) oscillations in pancreatic beta-cells.
胰岛素、胰岛素样生长因子及其他受体刺激的多种效应是通过磷脂第二信使磷脂酰肌醇-3,4,5-三磷酸（PIP(3)）介导的。PIP(3)由质膜中的磷酸肌醇3-激酶活性形成，在质膜中它用于募集信号蛋白。这些蛋白协调复杂的事件，导致细胞代谢、生长、运动和存活的变化。在过去十年中，测量单个活细胞质膜中PIP(3)的新技术显著提高了我们对这种信使在各种细胞过程中作用的理解。本综述总结了胰岛素反应性细胞中PIP(3)形成和降解所涉及的机制、如何在单个细胞中测量PIP(3)以及越来越多的证据表明，在许多类型的细胞中质膜PIP(3)浓度呈现复杂的时空模式，尤其着重于胰腺β细胞中自分泌胰岛素诱导的PIP(3)振荡。
