Regulation of insulin signalling & glucose homeostasis by protein tyrosine phosphatases

胰岛素信号传导的调节

• 批准号: nhmrc : 384146
• 负责人: Prof Tony Tiganis
• 金额: $ 33.59万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulation-insulin-signalling-tyrosine-phosphatases/97084
• 关键词: Regulation; insulin; signalling; glucose; homeostasis

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.

2型糖尿病已经达到流行病的比例，在西方社会中大约有6%的成年人口受到影响。尽管潜在的遗传原因和相关的病理症状是异质性的，但一个共同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是由于胰岛素受体（IR）信号传导的缺陷。IR是一种蛋白质酪氨酸激酶，其响应于胰岛素使自身和酪氨酸上的下游底物磷酸化。蛋白酪氨酸磷酸酶（PTPs），去磷酸化的IR及其底物可能是重要的目标，2型糖尿病的治疗干预;抑制特定的PTPs可能会允许增强胰岛素诱导的信号传导，以减轻胰岛素抵抗。该提案将研究PTPs，特别是TCPTP在体内IR信号传导中的作用。我们的研究将阐明IR调节和功能的分子机制，并可能为增强2型糖尿病胰岛素敏感性的新策略提供重要见解。