Type 2 diabetes causes significant health problems. The fundamental reasons underlying this disease are not fully known and will require molecular analysis of proteins critical to blood glucose control. This work aims to define a novel pathway that responds to circulating nutrients. The research will enhance our understanding of the links between diet and metabolic disease, with potential to reveal much needed therapeutic targets and/or dietary interventions for the treatment of Type 2 diabetes.
Cellular Mechanisms And Physiological Roles Of GLUT12 Mediated Glucose Transport In Glucose Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$499,000.00
Summary
Diabetes affects almost one million Australians, although only 50% are aware they have the disease. Type 2 diabetes accounts for about 90% of diabetes and usually occurs after the age of 40. As a leading cause of death, adult blindness, lower limb amputation, kidney failure, stroke and heart attack, diabetes has huge economic and social consequences and has been designated an Australian National Health priority. A clinical feature of Type 2 diabetes is high blood glucose levels. This occurs beca ....Diabetes affects almost one million Australians, although only 50% are aware they have the disease. Type 2 diabetes accounts for about 90% of diabetes and usually occurs after the age of 40. As a leading cause of death, adult blindness, lower limb amputation, kidney failure, stroke and heart attack, diabetes has huge economic and social consequences and has been designated an Australian National Health priority. A clinical feature of Type 2 diabetes is high blood glucose levels. This occurs because insulin does not effectively stimulate the transfer of glucose from the blood into muscle and fat. The reasons for this are not fully understood. Insulin normally works to move glucose transporter (GLUT) proteins to the surface of muscle and fat cells. One GLUT that has been studied extensively in muscle and fat is GLUT4. GLUT4 moves to the cell surface in response to insulin and this response is one of the defects that is known to occur in Type 2 diabetes. Glucose then accumulates in the blood, leading to many of the complications of diabetes. We have discovered a novel glucose transporter, GLUT12, that is also present in muscle and fat. We have shown that GLUT12, like GLUT4, responds to insulin. GLUT12 could therefore be a critical backup for GLUT4. We have also found that GLUT12 responds to glucose itself, suggesting a unique role in controlling blood glucose levels. We will explore how GLUT12 acts in muscle and fat cells to find whether GLUT12 can act as a backup for GLUT4. We will also study GLUT12 in tissue from normal animals and in animals with features of Type 2 diabetes. To determine the role of GLUT12 in maintaining normal blood glucose levels, we will produce mice with an inactive GLUT12 gene. Our research could identify novel ways of increasing GLUT12 activity. The eventual goal will be to find a pharmaceutical compound that can improve glucose transport into muscle, reduce high blood glucose levels and thus the complications of Type 2 diabetes.Read moreRead less
Regulation Of Glucose Uptake By Tropomyosins And Myosins
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
Defective import of glucose from the blood into fat and muscle is a key cause of adult-onset diabetes. We have identified a novel mechanical structure within muscle and fat cells defined by the protein tropomyosin that is involved in glucose import and potentially provides new targets for treatment of adult-onset diabetes and obesity.
Most common diseases of ageing like diabetes and cancer have proven intractable because much of our knowledge is limited to individual molecules. This proposal takes a global approach to complex diseases, utilising quantitative high-resolution methods and computational modelling. This research will lead to a completely new way of thinking about complex diseases providing a range of completely novel treatment options.