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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
Coronary Atherosclerosis And Its Relationship With Platelet Activation
Funder
National Health and Medical Research Council
Funding Amount
$101,039.00
Summary
Blood clots are critical to the development of heart attacks, which kill many thousands of Australians annually. Platelets are cells in the blood that play an essential role in formation of blood clots, and coronary disease is associated with platelet activation. This research study will investigate the nature of platelet activation in the arteries of the human heart, its relationship to activation of inflammatory cells, and to the severity of narrowings in the arteries of the human heart.
Time-domain Analysis Of Right Ventricular-pulmonary Arterial Coupling As A Windkessel And Wave System.
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
We seek to determine the number of people affected by pulmonary arterial hypertension (high blood pressure in the lungs) in Tasmania by collecting information from echocardiograms (heart ultrasounds). This is important because the incidence and prevalence is unknown but suspected to be unusually high in Tasmania. Also simultaneous pulmonary arterial pressure and velocity waves will be studied in humans to model pulmonary flow in an attempt to recognise pulmonary arterial hypertension earlier.
Retinal Vascular Structure And Function As Markers Of Endothelial Dysfunction.
Funder
National Health and Medical Research Council
Funding Amount
$104,664.00
Summary
Coronary heart disease (CHD) due to atherosclerosis (thickening of blood vessels) remains the leading cause of death in Australia, but visualisation of heart arteries usually requires invasive testing. Blood vessels in the eye (retina), can be viewed easily and may be indicative of blood vessel function in the heart and rest of the body. This study aims to explore the relationship between eye and heart blood vessels. Retinal imaging may thus enable earlier detection of patients at risk of CHD.
Evaluation Of Cardiac Risk And Alterations In Cardiovascular Structure And Function In Renal Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$72,275.00
Summary
Despite recent advances in health care, cardiovascular disease remains the leading killer of patients with Renal Failure and following Renal Transplantation. Current methods for assessing Cardiovascular Risk largely rely on tests that utilise radiation and-or kidney-toxic substances. Recent advances in Magnetic Resonance Imaging may allow for more accurate and safer assessment of Cardiovascular Risk and improve our understanding of the effect of Renal Transplantation on the Cardiovascular System
Central Control Of Blood Pressure: Neurotransmitters, Receptors, Signal Transduction And Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$941,350.00
Summary
The way that the brain controls blood pressure is of crucial significance to our day-to-day survival. Nerves in the lower brain and spinal cord cause blood pressure to be maintained at appropriate levels for all types of daily activities ranging from sleep, when blood pressure is very low, to exercise when blood pressure can be very high. In hypertension, a disorder that afflicts around 10% of the community, blood pressure is elevated to an extent that damages organs such as the brain, heart, ki ....The way that the brain controls blood pressure is of crucial significance to our day-to-day survival. Nerves in the lower brain and spinal cord cause blood pressure to be maintained at appropriate levels for all types of daily activities ranging from sleep, when blood pressure is very low, to exercise when blood pressure can be very high. In hypertension, a disorder that afflicts around 10% of the community, blood pressure is elevated to an extent that damages organs such as the brain, heart, kidney and eye. It now appears that most cases of hypertension have as their basis a disorder of the way that the brain, through the sympathetic nervous system, controls the heart and blood vessels. Many different brain systems need to change the way that blood is distributed in the body at different times. For example, when we eat, blood goes preferentially to our gut; if we exercise, to our heart and muscles; if we are cold, to our skin and when we think, to our brain. This specialised regulation of blood flow is accomplished by the interaction of nerves in the lower brain and spinal cord. It involves a vast array of special chemical messengers acting on specific receptors through different intracellular mechanisms and involving the turning on or off of genes. Only a few of these neurotransmitter systems are well understood. At the core of our proposal, we aim to determine which neurotransmitters systems are important for which cardiovascular functions. We anticipate that this new information will permit the development of new approaches to the management of hypertension. The reason for this is that since different pathways use different messenger systems, it should become possible to tailor therapy to suit hypertension without causing undesirable side-effects.Read moreRead less
A pressure pulse may be felt at the wrist with every heart beat. New technology allows the analysis of this pulse and provides information that may help doctors make decisions about a patients risk related to blood pressure as well as the effect of drug treatment. The research aims to determine the clinical significance of pressure pulse analysis at rest and during light exercise. It is expected that the new technology will improve the way people with high blood pressure are treated.
Does Pregnancy Cause Morphological Changes In Central As Well As Peripheral Nerve Pathways That Control Blood Pressure?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Pregnancy changes blood pressure but the mechanism is unknown. We will use state-of-the-art anatomical methods to define how pregnancy alters nerves controlling blood pressure. We will identify changes in the information the nerve cells receive, in their shape and in the way they communicate with other blood pressure-controlling nerve cells. This information will help to develop new ways to prevent and treat pre-eclampsia, a major cause of death and disability for mothers and their newborns.