Regulation of insulin signalling & glucose homeostasis by protein tyrosine phosphatases

2型糖尿病已经成为一种流行病，在西方社会大约有6%的成年人患有这种疾病。虽然潜在的遗传原因和相关的病理症状是不同的，但一个共同的特征是由于外周胰岛素抵抗引起的高血糖。胰岛素抵抗的分子基础被认为可归因于胰岛素受体（IR）信号传导的缺陷。IR是一种蛋白酪氨酸激酶，在胰岛素的作用下磷酸化自身和酪氨酸下游底物。使IR及其底物去磷酸化的蛋白酪氨酸磷酸酶（PTPs）可能是2型糖尿病治疗干预的重要靶点；抑制特定的ptp可能会增强胰岛素诱导的信号传导，从而减轻胰岛素抵抗。本提案将研究PTPs，特别是TCPTP在体内IR信号传导中的作用。我们的研究将揭示IR调节和功能的分子机制，并可能为提高2型糖尿病胰岛素敏感性的新策略提供重要见解。

Type 2 diabetes has reached epidemic proportions afflicting roughly 6% of the adult population in Western society. Although the underlying genetic causes and the associated pathological symptoms are heterogenous, a common feature is high blood glucose due to peripheral insulin resistance. The molecular basis of insulin resistance is believed to be attributable to defects in insulin receptor (IR) signalling. The IR is a protein tyrosine kinase that phosphorylates itself and downstream substrates on tyrosine in response to insulin. Protein tyrosine phosphatases (PTPs) that dephosphorylate the IR and its substrates might be important targets for therapeutic intervention in type 2 diabetes; inhibition of specific PTPs may allow for enhanced insulin-induced signalling to alleviate insulin resistance. This proposal will examine the roles of PTPs and in particular TCPTP in IR signalling in vivo. Our studies will shed light on the molecular mechanisms of IR regulation and function and may provide important insights into novel strategies for enhancing insulin sensitivity in type 2 diabetes.