SHIP-2 regulation of the actin cytoskeleton

餐后，葡萄糖在血液中循环，并通过细胞内葡萄糖转运蛋白从细胞内部移动而被吸收到细胞中，以与细胞膜融合，随后将葡萄糖转移到细胞中。这个过程是由胰岛素触发的。由于这种细胞过程的失败而导致的最常见的疾病之一是糖尿病。在澳大利亚许多成年人中发生的一种常见的糖尿病是由胰岛素抵抗引起的，胰岛素的作用减弱，细胞越来越不能摄取葡萄糖。最近的研究表明，一种称为SHIP-2的新型酶可能在调节细胞中的胰岛素作用中发挥作用。小鼠中SHIP-2的缺失导致这些动物对胰岛素的敏感性增加，血糖水平降低，并且响应于低剂量胰岛素而在细胞中摄取葡萄糖的能力大大增强。我们的实验室一直致力于研究SHIP-2功能的细胞机制。我们最近揭示了SHIP-2的细胞内定位，并证明了SHIP-2是如何定位在细胞中的。这些研究表明，SHIP-2通过与其他蛋白质的相互作用，调节细胞膜下的肌动蛋白细胞骨架，这可能是促进细胞葡萄糖摄取的机制。这项研究计划旨在确定SHIP-2如何促进葡萄糖摄取到细胞中。我们将建立高水平表达这种酶的细胞系和转基因动物，并确定胰岛素刺激葡萄糖摄取的功能后果。总的来说，这些长期研究可能有助于糖尿病患者更好的治疗策略。

Following a meal glucose circulates in the blood and is taken up into cells via movement of an intracellular glucose transporter from the inside of the cell to fuse with the cell membrane and subsequent transfer of the glucose into the cell. This process is triggered by insulin. One of the commonest diseases resulting from a failure of this cellular process is diabetes. A common form of diabetes which occurs in many adults in Australia results from insulin resistance, whereby the effects of insulin are diminished and cells become increasingly unable to uptake glucose. Recent studies have demonstrated that a novel enzyme known as SHIP-2 may play a role in regulating insulin action in cells. Deletion of SHIP-2 in mice results in these animals have increased sensitivity to insulin, low blood glucose levels, and a greatly enhanced ability to take up glucose in cells in response to low dose insulin. Our laboratory has been working on the cellular mechanisms regulating SHIP-2 function. We have recently revealed the intracellular location of SHIP-2 and also demonstrated how SHIP-2 is localized in the cell. These studies have shown that SHIP-2, via interactions with other proteins, regulates the actin cytoskeleton immediately beneath the cell membrane and this may be a mechanism for facilitating cellular glucose uptake. This research proposal aims to determine how SHIP-2 facilitates glucose uptake into cells. We will make cell lines and transgenic animals which express high levels of this enzyme and determine the functional consequences on insulin stimulated glucose uptake. Collectively these studies in the long term may facilitate better treatment strategies for diabetic patients.