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
Assessment Of The Mechanisms Involved And Severity Of Arterial Disease In Insulin Resistant States
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Type 2 Diabetes is a major risk factor towards atherosclerosis or blood vessel narrowing. This can lead to vascular complications such as heart attacks, strokes and amputations. This research aim to examine the relationship between some of the mechanisms and their contribution towards vascular disease in the progression from normal health, through insulin resistance to diabetes. This understanding will provide diagnostic tools and treatment targets for diabetic vascular disease.
Novel Therapeutic Interventions To Increase Blood Flow To Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$360,750.00
Summary
Over the past decade it has become clear that the cytokine interleukin (IL)-6 is produced in and released from tissues such as fat and muscle to mediate metabolic processes. In this respect, it acts in a hormone like manner. During this period it has also become apparent that the hormone insulin increases blood flow to skeletal muscle. There is emerging evidence that IL-6 plays a role, not only in metabolic and signalling processes within skeletal muscle, but also in blood flow. This project wil ....Over the past decade it has become clear that the cytokine interleukin (IL)-6 is produced in and released from tissues such as fat and muscle to mediate metabolic processes. In this respect, it acts in a hormone like manner. During this period it has also become apparent that the hormone insulin increases blood flow to skeletal muscle. There is emerging evidence that IL-6 plays a role, not only in metabolic and signalling processes within skeletal muscle, but also in blood flow. This project will determine whether the cytokine IL-6 is a viable therapeutic target in the treatment of blood flow disorders in patients with type 2 diabetes. This has major ramifications since type 2 diabetes has reached pandemic levels in Australia and is estimated to cost the community approximately 800 million dollars per year.Read moreRead less