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

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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.