Actions Of The Polyphenol Epigallocatechin 3-gallate On Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$409,746.00
Summary
This project will determine whether the bioactive compound in green tea (called EGCG) can reduce insulin resistance by enhancing the ability of insulin to open very small blood vessels (called capillaries) in muscle. Opening more capillaries will help glucose to be stored in muscle, thus alleviating insulin resistance. Findings from these studies may have important impact on the management of insulin resistance and type 2 diabetes.
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
Mechanisms Linking Insulin-mediated Muscle Capillary Recruitment And Glucose Uptake
Funder
National Health and Medical Research Council
Funding Amount
$315,990.00
Summary
A number of studies over recent years including our own have suggested that insulin acts in normal humans and animals to improve blood supply to muscle and that a contributing factor to Type 2 diabetes is an impaired ability of insulin to achieve this effect. Our key contribution to this field is the finding that insulin acts to alter blood flow in muscle to improve access for itself and nutrients such as glucose. This discovery of blood flow redistribution in muscle was made possible by newly d ....A number of studies over recent years including our own have suggested that insulin acts in normal humans and animals to improve blood supply to muscle and that a contributing factor to Type 2 diabetes is an impaired ability of insulin to achieve this effect. Our key contribution to this field is the finding that insulin acts to alter blood flow in muscle to improve access for itself and nutrients such as glucose. This discovery of blood flow redistribution in muscle was made possible by newly developed in-house methods. Using these methods we now wish to explore (a) the mechanism by which insulin mediates this effect and (b) when this effect of insulin to improve muscle blood flow is impaired in diabetes, how it might be recovered. We expect to find that insulin-mediated capillary recruitment in muscle results from a signal substance released from muscle that permeates nearby tissue reacting with the blood vessels to improve blood flow. It is also expected that new therapeutic approaches for enhancing insulin action in muscle and targeted at the blood vessels will be identified.Read moreRead less
Cyclic GMP Phosphodiesterase Inhibitors And Facilitation Of Insulin-mediated Capillary Recruitment In Muscle
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
It would now seem clear that insulin has a major stimulatory effect on blood flow within muscle to improve access for itself as well as nutrients such as glucose. When this haemodynamic effect of insulin is impaired insulin resistance in terms of glucose uptake by muscle results and there is the potential for type 2 diabetes to develop. Our key contribution has been the development of new techniques to make this observation possible and it would be fair to say that we are the world leaders in th ....It would now seem clear that insulin has a major stimulatory effect on blood flow within muscle to improve access for itself as well as nutrients such as glucose. When this haemodynamic effect of insulin is impaired insulin resistance in terms of glucose uptake by muscle results and there is the potential for type 2 diabetes to develop. Our key contribution has been the development of new techniques to make this observation possible and it would be fair to say that we are the world leaders in this field because of these techniques. Using these methods we now wish to develop new drugs for treating type 2 diabetes based on improving muscle capillary blood flow. The approach we will use is similar to that used previously by others for the treatment of erectile dysfunction with drugs targeted at a particular enzyme controlling the metabolism of a substance (cyclic GMP) which in turn regulates blood flow to the corpus cavernosum. In our case, the drugs will be targeted at another specific isoform of the same enzyme, cyclic GMP phosphodiesterase, located at control points in the skeletal muscle microvasculature. We expect to find that insulin-mediated capillary recruitment in muscle will be enhanced by such drugs. As a consequence, insulin resistance in muscle will be lessened.Read moreRead less
The Coronary Vascular Bed, Shear Stress, Endothelial Signalling And Myocyte Electrophysiology
Funder
National Health and Medical Research Council
Funding Amount
$133,774.00
Summary
Physiologic control muscle performance includes a little understood signal from the walls of blood vessels stimulated by pressure and flow which effect muscle function. How this signal operates is controversial. We have developed a model which enables the evaluation of such signalling where changes in flow in the circumflex coronary artery induce easily measured local changes in electrophysiology which are confined to the territory of the circumflex coronary artery and which can be compared with ....Physiologic control muscle performance includes a little understood signal from the walls of blood vessels stimulated by pressure and flow which effect muscle function. How this signal operates is controversial. We have developed a model which enables the evaluation of such signalling where changes in flow in the circumflex coronary artery induce easily measured local changes in electrophysiology which are confined to the territory of the circumflex coronary artery and which can be compared with control values from the left anterior descending coronary artery territory. We propose to use this stable model to evaluate the origin, the transmission agent and the mechanism by which it alters the action potential duration.Read moreRead less
Insulin Resistance In Peripheral Artery Disease: Clinical Significance And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
This project seeks to improve our understanding and treatment of peripheral artery disease – a condition caused by narrowing/blockages in arteries that supply the legs. Peripheral artery disease affects ~15% of adults >40 years and often causes severe, disabling leg pains during walking. Building on recent findings that peripheral artery disease shares some similar characteristics to type 2 diabetes (“insulin resistance”), a common anti-diabetes drug will be trialled as a potential new strate ....This project seeks to improve our understanding and treatment of peripheral artery disease – a condition caused by narrowing/blockages in arteries that supply the legs. Peripheral artery disease affects ~15% of adults >40 years and often causes severe, disabling leg pains during walking. Building on recent findings that peripheral artery disease shares some similar characteristics to type 2 diabetes (“insulin resistance”), a common anti-diabetes drug will be trialled as a potential new strategy to alleviate these leg pains.Read moreRead less