A novel mechanism for manipulation of peripheral glucose utilization in patients with type 2 diabetes mellitus.

意义：超过60万澳大利亚人患有2型糖尿病(大约一半未确诊)，据估计，这一数字在未来10年将大幅增加到成年人口的10%。在这项资助结束时，我们希望了解特定的信号分子是否可能可信地代表一种控制血糖的新治疗方法的基础。如果成功，这项工作可能有助于通过新的降糖剂改善代谢控制和预防糖尿病并发症。假设：肌肉是体内葡萄糖处理的主要场所，与肌肉摄取葡萄糖最相关的两个刺激因素是胰岛素和肌肉收缩(运动)。2型糖尿病患者的胰岛素途径受损，导致高血糖和并发症。然而，在2型糖尿病患者中，运动引起的葡萄糖摄取似乎是正常的。事实上，我们有证据表明，这一途径可能会补偿2型糖尿病患者受损的胰岛素作用。我们假设，收缩(运动)激活的分子可能有助于改善2型糖尿病患者的静息血糖控制。目的：我们计划进行一系列的三项研究，以检验运动介导的葡萄糖摄取中的一种制剂是否可以显著和长期地改善静息状态下的葡萄糖摄取。

Significance: Over 600,000 Australians have type 2 diabetes (approximately half are undiagnosed) and it is estimated that this number will increase substantially to 10% of the adult population over the next 10 years. At the conclusion of this grant we expect to understand whether specific signalling molecules might plausibly represent the basis of a novel therapeutic approach to control blood glucose. If successful, this work could contribute to improved metabolic control and prevention of diabetic complications through new blood glucose lowering agents. Hypotheses: Muscle is the major site of glucose disposal in the body and the two most relevant stimuli for glucose uptake into muscle are insulin and muscle contraction (exercise). The insulin pathway is impaired in patients with type 2 diabetes leading to high blood glucose and complications. Glucose uptake in response to exercise however appears to be normal in patients with type 2 diabetes. Indeed we have evidence to suggest that this pathway may compensate for impaired insulin action in type 2 diabetes. We hypothesise that molecules activated by contraction (exercise) may be useful as therapies to improve resting glucose control in type 2 diabetic patients. Aims: We plan a series of three studies to examine whether glucose uptake may be improved both acutely and chronically at rest by an agent implicated in exercise mediated glucose uptake.