Understanding The Metabolic Consequences Of Impaired AMPKa2 And NNOS� In Skeletal Muscle: Implications For The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$575,527.00
Summary
The inability of muscle to utilise sugar from the blood is a major problem that contributes to obesity and Type 2 diabetes. Since the number of people with these diseases will at least double by 2030, we need to find out what causes this problem. We will examine whether two muscle proteins that are impaired in obesity and Type 2 diabetes are also responsible for impaired sugar utilisation. We think that increasing these muscle proteins will fix the _sugar problem�, and remedy these diseases.
Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will ass ....Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will assess the impact of acute and chronic changes in wall flow and shear on arterial size and function. We will also develop new software which measures other aspects of artery wall behaviour. These basic human physiology studies have direct implications for assessment of artery health in humans.Read moreRead less
Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old musc ....Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old muscles young again, is a research strategy that will promote healthy ageing and enable older Australians to enjoy a better quality of life.Read moreRead less
Examining the links between obesity and insulin resistance. Obesity prevalence is rapidly increasing in Australia and contributes to the onset of many chronic diseases, such as diabetes, heart disease and cancer. This project will examine how obesity contributes to disease risk and how modifying nutrient delivery and other interventions that protect from cellular stress reduces these risks.
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less
Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard ....Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard tail), to describe the regrowth process and determine the abundance, location, functional properties and molecular control of the new lymphatics. Furthermore, if reptilian lymphatic growth factors can promote lymphangiogenesis in mammals, we can design novel therapeutic approaches using reptilian ligands to promote lymphangiogenesis in lymphoedematous human tissues.Read moreRead less
Unified framework of intestinal motility. The project aims to establish how a few fundamental mechanisms determine the large repertoire of intestinal motor patterns responsible for moving nutrients along the digestive tract. The project will combine experimental and theoretical data, with biomechanical and electrophysiological models to create a new understanding of this essential function of the body.
Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount ....Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount before we can understand and develop treatments for dealing with heart problems. This information will facilitate the development of techniques to treat and prevent heart rhythm disorders that are a common cause of morbidity in the community.Read moreRead less
Does muscle contribute to the maintenance of vitamin D status in winter? This project aims to test the mechanism by which vitamin D status is maintained in winter when input is low. The long half-life in blood of the vitamin D metabolite, 25-hydroxyvitamin D [25(OH)D], maintains an adequate vitamin D status over winter, when sunlight, which produces vitamin D in skin, is reduced. From preliminary data in sheep and mice, this project proposes that skeletal muscle, not fat, stores vitamin D. This ....Does muscle contribute to the maintenance of vitamin D status in winter? This project aims to test the mechanism by which vitamin D status is maintained in winter when input is low. The long half-life in blood of the vitamin D metabolite, 25-hydroxyvitamin D [25(OH)D], maintains an adequate vitamin D status over winter, when sunlight, which produces vitamin D in skin, is reduced. From preliminary data in sheep and mice, this project proposes that skeletal muscle, not fat, stores vitamin D. This project will test this hypothesis in sheep, cultured muscle cells and in transgenic mice. The project will confirm whether the processes identified in skeletal muscle contribute to the maintenance of vitamin D status, and identify ways of enhancing this process.Read moreRead less
Urinary continence and incontinence in men: New insight through new technologies. Healthy ageing in men is largely overlooked. Disorders of continence are surprisingly common with increasing age, and are socially debilitating. To understand changes in continence and address healthy ageing it is first necessary to gain an understanding of continence mechanisms in healthy men. Continence in women has received wide attention, but anatomy and function differ, as do the challenges throughout life (ch ....Urinary continence and incontinence in men: New insight through new technologies. Healthy ageing in men is largely overlooked. Disorders of continence are surprisingly common with increasing age, and are socially debilitating. To understand changes in continence and address healthy ageing it is first necessary to gain an understanding of continence mechanisms in healthy men. Continence in women has received wide attention, but anatomy and function differ, as do the challenges throughout life (childbirth vs. prostate disease). Using novel methods we will test a new hypothesis of male continence with the goal to provide new physiological discoveries, new methods, and baseline data upon which strategies to enhance healthy ageing and reduce the economic burden of disorders of continence can be developed and refined. Read moreRead less