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

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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.