Novel Metabolic Actions of HDL with Potential Therapeutic Implications for Type 2 Diabetes and the Metabolic Syndrome.

目前世界上有超过1.7亿患者被诊断患有2型（迟发性）糖尿病，预计到2030年这一数字将翻一番。几乎每四个25岁及以上的澳大利亚人中就有一个患有糖尿病或葡萄糖代谢受损。这些情况在个人痛苦和经济负担方面造成了严重问题。不良的饮食习惯、久坐不动的生活方式导致体重增加和肥胖率增加是2型糖尿病患病率不断上升的原因。我们的提案调查了一种治疗这些疾病的新方法。我们已经确定了HDL（好）胆固醇与人体肌肉细胞中葡萄糖和脂肪代谢之间的重要联系。我们已经证明，HDL增加了肌肉细胞对葡萄糖的摄取。这一过程预计将从血管中去除葡萄糖，在那里它会导致最终导致心脏病发作和中风的损伤。此外，我们已经证明HDL增加了身体使用的脂肪量。因此，HDL不仅可以从血管中清除有害脂肪，还有助于减轻体重。我们的研究旨在确定这些机制在健康个体和2型糖尿病患者中的相关性。在这项资助的结论中，我们希望了解HDL升高策略是否可能是2型糖尿病的有效新疗法。具体来说，我们将了解：1。高密度脂蛋白如何发挥其有益作用; 2.急性和慢性高密度脂蛋白升高是否使用药物改善人体的葡萄糖和脂肪代谢。

There are currently in excess of 170 million patients diagnosed with type 2 (late onset) diabetes in the world and this figure is expected to double by 2030. Almost one in four Australians 25 years and over has either diabetes or a condition of impaired glucose metabolism. These conditions pose significant problems in terms of both individual suffering and economic burden. Poor diet, sedentary lifestyles with resultant weight gain and increased obesity rates underlie the escalating prevalence of type 2 diabetes. Our proposal investigates a novel approach to treat these conditions. We have identified an important link between HDL (good) cholesterol and glucose and fat metabolism in human muscle cells. We have shown that HDL increases glucose uptake into muscle cells. This process would be expected to remove glucose from blood vessels where it causes damage which ultimately contributes to heart attack and stroke. Furthermore, we have shown that HDL increases the amount of fat the body uses. HDL may therefore not only remove damaging fat from blood vessels, but also help to reduce body weight. Our study seeks to determine the relevance of these mechanisms in both healthy individuals and patients with type 2 diabetes. At the conclusion of this grant we expect to understand whether HDL raising strategies may be a an effective new therapy for type 2 diabetes. Specifically, we will understand: 1. how HDL exerts its beneficial effects and 2. whether acute and chronic HDL elevation using drugs improves glucose and fat metabolism in humans.