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Echocardiographic Predictors Of Cardiovascular Outcomes And Their Progression In Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$104,664.00
Summary
Premature cardiovascular (CV) disease is the most common cause of death in diabetes, and the risk persists even after adjustment for traditional risk factors. We aim to assess the prevalence and predictors of CV disease in type 2 diabetes (DM). Additionally we will assess the prognostic utility of potential plasma biomarkers and echocardiography, perform a 8-year outcome analysis.
Biomarkers And Genetic Determinants Of Cardiovascular Risk In Diabetes: The FIELD Study
Funder
National Health and Medical Research Council
Funding Amount
$1,961,718.00
Summary
The patient characteristics and blood factors determining the risk of heart attack, stroke, kidney and eye disease in people suffering from diabetes are not well understood. The FIELD Study, by analysing these characteristics and many blood factors hopes to shed light on ways to prevent these complications for future patients. The project proposes to measure factors on blood samples collected on more than 9000 patients with diabetes and analyse these over the next three years. It hopes to help d ....The patient characteristics and blood factors determining the risk of heart attack, stroke, kidney and eye disease in people suffering from diabetes are not well understood. The FIELD Study, by analysing these characteristics and many blood factors hopes to shed light on ways to prevent these complications for future patients. The project proposes to measure factors on blood samples collected on more than 9000 patients with diabetes and analyse these over the next three years. It hopes to help doctors identify patients who are at particular risk of complications for special attention and early treatment.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.
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
EGF Receptor Transactivation In GPCR-mediated Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$710,625.00
Summary
Soon after birth, the muscle cells of the human heart stop dividing and subsequent growth of the heart occurs through enlargement of pre-existing muscle cells in a process referred to as hypertrophy. This normal growth accounts for the difference in size between juvenile and adult human hearts. In certain people, heart cell growth is accelerated as a consequence of complex genetic, hormonal and environmental factors. In others, it occurs as an adaptive response to high blood pressure or damage-d ....Soon after birth, the muscle cells of the human heart stop dividing and subsequent growth of the heart occurs through enlargement of pre-existing muscle cells in a process referred to as hypertrophy. This normal growth accounts for the difference in size between juvenile and adult human hearts. In certain people, heart cell growth is accelerated as a consequence of complex genetic, hormonal and environmental factors. In others, it occurs as an adaptive response to high blood pressure or damage-disease of the heart muscle, such as occurs following a heart attack. As hearts grow inappropriately, they function less efficiently and eventually fail. Cardiac hypertrophy is therefore a major risk factor for heart failure and death. Hormones like adrenalin, angiotensin, and endothelin affect cells of the heart and blood vessels to regulate blood pressure and volume. In addition, these hormones also act directly on heart cells to cause growth, particularly during the accelerated phase associated with cardiac hypertrophy. One attribute shared by these hormones is that they act through G-protein coupled receptors (GPCRs), a superfamily of cell surface proteins. How binding of hormone to its specific GPCR triggers cell growth has been the focus of extensive research. Based on studies of angiotensin receptors in cultured muscle cells, we have observed that the growth action of angiotensin receptors requires them to first hijack another receptor - the epidermal growth factor receptor. By commandeering the EGF receptor, the angiotensin hormone in effect usurps growth-signalling pathways. This application proposes experiments that will investigate the mechanism and consequence of GPCRs stimulation of EGF receptors in heart cells and whole animals. By understanding the mechanism by which angiotensin promotes growth, better therapeutic regimens against abnormal growth of the heart during human cardiovascular disease will evolve.Read moreRead less
Muscle cells that constitute the bulk of the human heart do not divide but enlarge as we grow. Accelerated heart cell growth, as a consequence of heart damage or other factors, is a predictor of heart failure and early death. This application examines the cellular events that control heart growth in response to angiotensin, a hormone linked to heart failure. By understanding the mechanism by which angiotensin promotes growth, better therapies against human cardiovascular disease will evolve.