Protein tyrosine phosphatases in the regulation of insulin receptor signalling and glucose uptake

II型糖尿病的主要病理特征是细胞对正常水平的循环胰岛素缺乏反应。胰岛素与其细胞表面的跨膜受体结合，启动一系列称为细胞信号的事件，导致葡萄糖的摄取等。蛋白酪氨酸磷酸酶(PTPs)是胰岛素诱导的信号转导过程中的关键负性调节因子，用广谱的化学抑制剂抑制PTPs可以在正常和糖尿病大鼠体内模拟胰岛素的多种作用和降低血糖水平。这项建议将研究PTPs，特别是TCPTP和PTP1B在胰岛素受体介导的信号和葡萄糖摄取中的作用。此外，我们还将探索TCPTP在胰岛素受体非依赖性葡萄糖摄取交替过程中的作用。我们的研究将阐明葡萄糖摄取调节的重要过程。此外，我们的研究可能会导致能够抑制PTPs的药物的开发，如TCPTP，这可能允许增强葡萄糖摄取，并在治疗II型糖尿病中具有治疗作用。

The key pathological feature of type II diabetes is the lack of cellular response to normal levels of circulating insulin. Insulin binding to its cell surface transmembrane receptor initiates a cascade of events known as cellular signalling that results in amongst other things in the uptake of glucose. Protein tyrosine phosphatases (PTPs) are key negative regulators of insulin-induced signalling events and their inhibition with broad based chemical inhibitors can mimic several actions of insulin and lower blood glucose levels in both normal and diabetic rats. This proposal will examine the roles of PTPs and in particular TCPTP and PTP1B in insulin receptor-mediated signalling and glucose uptake. Moreover we will explore the role of TCPTP in alternate insulin receptor-independent processes for glucose uptake. Our studies will shed light on processes important for the regulation of glucose uptake. Moreover our studies may lead to the development of drugs capable of inhibiting PTPs such as TCPTP, that may allow for enhanced glucose uptake and have therapeutic use in the treatment of type II diabetes.