Microvascular Complications Of Diabetes - Potential Role Of Regenerative Therapies
Funder
National Health and Medical Research Council
Funding Amount
$32,003.00
Summary
The global burden of diabetes is projected to reach more than 366 million by 2025. According to the AusDiab 2005 study, each year 0.8% of Australians develop diabetes. Diabetes is the leading cause of end-stage kidney disease in Australia. Current treatments slow damage to the kidney, but do not reverse kidney damage. We will explore the potential for adult progenitor cells (endothelial progenitor cells) to reverse damage to the kidney and restore its function.
The Role Of The Endothelium In Insulin's In Vivo Action Upon Skeletal Muscle Metabolism.
Funder
National Health and Medical Research Council
Funding Amount
$451,500.00
Summary
A number of studies using novel techniques developed in association with our USA collaborators, indicate that insulin has a major stimulatory effect on blood flow within muscle in both animals and humans to improve access for itself as well as nutrients such as glucose. As much as 50% of the glucose taken up by muscle in vivo during continual exposure to insulin may be attributed to this effect. Moreover, this haemodynamic effect of insulin in muscle is impaired in a number of animal models and ....A number of studies using novel techniques developed in association with our USA collaborators, indicate that insulin has a major stimulatory effect on blood flow within muscle in both animals and humans to improve access for itself as well as nutrients such as glucose. As much as 50% of the glucose taken up by muscle in vivo during continual exposure to insulin may be attributed to this effect. Moreover, this haemodynamic effect of insulin in muscle is impaired in a number of animal models and in obese humans when insulin mediated muscle glucose uptake is also impaired. What is not known is how insulin mediates this haemodynamic effect of recruiting capillary blood flow. Thus in the present study a number of aspects are to be explored, with particular focus on the cells that line the blood vessels and constitute the capillaries, the so called endothelium. First, we will explore the specific role of the endothelium in insulin's action by using the novel approach of attaching insulin to a large molecule that prevents it leaving the lumen of the blood vessel. This will mean that insulin will be confined to interacting only with insulin receptors on the muscle endothelium. Similarly, non activating anti insulin receptor antibody will be used in the presence of insulin to selectively prevent activation of the endothelial insulin receptors. In addition, we will investigate whether homocysteine, an amino acid found to impair endothelial dependent vasodilatation, impairs the haemodynamic effects of insulin. The impact that normal insulin release after a meal has upon the haemodynamic actions in muscle and the role this has in muscle glucose uptake will also be investigated by using the techniques developed in the first part of the project. Our over riding hypothesis is that the endothelium plays a key role in controlling insulin and possibly glucose access to muscle cells and thus a significant proportion of insulin mediated metabolic events in muscle.Read moreRead less