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 Insulin Hypersecretion In Beta Cell Dysfunction In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$318,622.00
Summary
The treatment of diabetes involves the use of drugs that stimulate the release of insulin from the pancreas to reduce the high blood sugar levels. However, we believe that while in the short term this is a good strategy, in the long-term it damages the cells that produce insulin leading to a worsening state of diabetes. It is the aim of this application to understand the mechanisms by which the insulin producing cells are damaged when forced to oversecrete insulin.
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
Defining Vascular Health And Modifiable Risk Factors Over Time In Childhood.
Funder
National Health and Medical Research Council
Funding Amount
$368,061.00
Summary
Adult heart disease and strokes have their origin in childhood. We will follow healthy children and children with diabetes or obesity over 2 years during puberty when blood vessel disease is detectable. We will define which are the most sensitive markers of blood vessel disease and the continuum of risk factors. This is essential knowledge to best define children at risk and to test clinical and public health interventions.
Reproduction is controlled by the brain through the hormone gonadotropin releasing hormone (GnRH). Leptin from fat acts on the brain to 'inform' GnRH cells of metabolic state; low levels signal lack of energy stores and suppress reproduction. Leptin treatment of lean individuals restores reproductive function, but the mechanism is not clear. Our data implicate the melanocortins as a means of transmitting information on metabolic state to GnRH cells and the project investigates this pathway.