Exercise As Medicine For Heart Failure: A Novel Intervention To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$665,585.00
Summary
Heart failure (HF) is a common, debilitating and expensive disease; prognosis remains poorer than for the most cancers. 30,000 Australians are diagnosed every year and 300,000 live with the HF, at an annual cost of ~$1Billion. Exercise training is effective therapy in HF, because it reverses many of the problems that contribute to the reduced lifespan and impaired quality of life of patients with HF. We will test an exciting new type of exercise that promising greater benefit, at lower risk.
Does Exercise Increase Skeletal Muscle Insulin Sensitivity Via Nitric Oxide?
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
Almost one in four Australian adults have either diabetes or impaired glucose metabolism. A major benefit of exercise is that it increases the sensitivity of muscle to insulin for many hours after the exercise is completed. We don't fully understand the mechanisms that exercise increases muscle insulin sensitivity. If we discover how nitric oxide production during exercise is involved, drugs that mimic these exercise effects may be designed to benefit those with diabetes.
Intracellular calcium in intact muscle during fatigue and stretch-induced damage. Confocal microscopes can investigate intact tissues during normal function. We will develop and apply this novel approach to muscle. We expect this new approach to become a fundamental new tool for exploring muscle function under near normal conditions. Muscle pain and weakness are common disabilities in humans and we expect this new approach to provide insights into the causes and treatment of these common cond ....Intracellular calcium in intact muscle during fatigue and stretch-induced damage. Confocal microscopes can investigate intact tissues during normal function. We will develop and apply this novel approach to muscle. We expect this new approach to become a fundamental new tool for exploring muscle function under near normal conditions. Muscle pain and weakness are common disabilities in humans and we expect this new approach to provide insights into the causes and treatment of these common conditions.Read moreRead less
Regulation Of Skeletal Muscle AMP-activated Protein Kinase By Glycogen
Funder
National Health and Medical Research Council
Funding Amount
$561,558.00
Summary
The enzyme AMP protein kinase has three parts (subunits) and is central to controlling the body's metabolism. We have discovered that one subunit is essential for tightly associating the enzyme with muscle glycogen which is a source of high energy and efficient metabolism. We will identify where the enzyme attaches to glycogen, and how diet and exercise alter this association. Understanding this could lead to new approaches for treating Type 2 diabetes where energy metabolism is disrupted.
IS NITRIC OXIDE A CENTRAL REGULATOR OF EXERCISE-INDUCED SKELETAL MUSCLE MITOCHONDRIAL BIOGENESIS?
Funder
National Health and Medical Research Council
Funding Amount
$340,750.00
Summary
Mitochondria are the energy producing parts of the cell and are the major controllers of metabolism. There is now good evidence that reduced muscle mitochondrial size contributes to diabetes. Exercise is good for diabetics due partly to increasing muscle mitochondrial production (mitochondrial biogenesis). Unfortunately, little is known about the mechanisms involved in increased muscle mitochondrial biogenesis following exercise. It has been shown recently that nitric oxide (NO), a gas made by m ....Mitochondria are the energy producing parts of the cell and are the major controllers of metabolism. There is now good evidence that reduced muscle mitochondrial size contributes to diabetes. Exercise is good for diabetics due partly to increasing muscle mitochondrial production (mitochondrial biogenesis). Unfortunately, little is known about the mechanisms involved in increased muscle mitochondrial biogenesis following exercise. It has been shown recently that nitric oxide (NO), a gas made by muscle during exercise, plays a role in mitochondrial biogenesis in fat cells. This project will determine whether NO is a central regulator of exercise-induced mitochondrial biogenesis in skeletal muscle. If we find that NO increases mitochondrial biogenesis in muscle, drugs designed to mimic these exercise effects may prevent or improve diabetes. We will firstly establish if specific drug treatments that alter NO levels in muscle cells grown in culture alter mitochondrial biogenesis. These results will help us to clarify the role of NO in mitochondrial biogenesis. However, it is difficult to directly examine the effects of exercise in cultured cells. Therefore, further studies will then use real life models such as rodents that have been exercised to examine the role of NO and exercise on mitochondrial biogenesis. We will feed a drug to decrease NO levels in normal rats; and use mice, genetically altered to be lacking in NO to determine if these treatments decrease mitochondrial biogenesis that is normally seen following endurance exercise. Furthermore, since defects in mitochondrial biogenesis have such an important impact on diabetic humans, we will use humans to examine if differences in NO levels in skeletal muscle among type 2 diabetics or endurance-trained athletes correlate with mitochondrial biogenesis. Finally, we will infuse a drug into type 2 diabetics that increases NO in muscle to determine if it also increases mitochondrial biogenesis.Read moreRead less
The grand challenge of predicting human movement energetics. This Project aims to advance our understanding of how the neuromuscular system uses energy during movement by exploring the interplay of different factors that influence movement energetics. The Project will explore different levels of organisation; from how muscle fibres consume energy to how those fibres interact and are subsequently controlled within a complex neuromuscular system. Expected outcomes of this Project will be an improv ....The grand challenge of predicting human movement energetics. This Project aims to advance our understanding of how the neuromuscular system uses energy during movement by exploring the interplay of different factors that influence movement energetics. The Project will explore different levels of organisation; from how muscle fibres consume energy to how those fibres interact and are subsequently controlled within a complex neuromuscular system. Expected outcomes of this Project will be an improved capacity to predict energy expenditure of the vast array of movements that humans perform. This will enable accurate monitoring of human energy expenditure and will provide benefits for individualised exercise prescription, enhancing work productivity or designing devices to augment human performance.Read moreRead less