Central And Peripheral Actions Of Insulin For The Control Of Muscle Capillary Recruitment
Funder
National Health and Medical Research Council
Funding Amount
$433,973.00
Summary
Type 2 diabetes is on the increase world wide and reflects the ever-increasing incidence of obesity. Whereas the likely cause of type 2 diabetes includes low physical activity and high fat diet, the primary metabolic abnormality is likely to be muscle insulin resistance. The cause of this resistance is controversial, but may stem from microvascular dysfunction where muscle becomes poorly perfused and unresponsive to the action of insulin to recruit capillary flow. In this project we will further ....Type 2 diabetes is on the increase world wide and reflects the ever-increasing incidence of obesity. Whereas the likely cause of type 2 diabetes includes low physical activity and high fat diet, the primary metabolic abnormality is likely to be muscle insulin resistance. The cause of this resistance is controversial, but may stem from microvascular dysfunction where muscle becomes poorly perfused and unresponsive to the action of insulin to recruit capillary flow. In this project we will further extend our seminal discoveries that insulin mediates capillary recruitment under normal circumstances and that in various models of insulin resistance insulin's ability to increase the perfusion of muscle is markedly impaired. We will explore the hypothesis, that insulin controls microvascular perfusion of muscle by a central neural mechanism ending at terminal arterioles on the vasculature and endeavour to identify the details of this control. We will use in-house novel techniques for examining both the role of central control mechanisms involving the brain as well as peripheral mechanisms by local infusion of various agents likely to either enhance or block insulin's microvascular action. A positive outcome will enhance our understanding of insulin action and the insulin resistance that precedes type 2 diabetes. There is also the possible outcome that important clues will be obtained leading to new therapeutic agents that could be used to treat type 2 diabetes.Read moreRead less
Accelerated Telomere Length Attrition Rate In Diabetes And Its Cellular Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$38,381.00
Summary
I am a PhD in Medicine-University of Sydney. My research focus is about telomere dynamic, its mechanism and correlation between telomere length and diabetes attributes. I will compare telomere length between different diabetes groups & examine telomere regulation in cell culture/animal model to compliment my clinical data. The hypothesis: accelerated telomere shortening may co-segregate with diabetes complications and by preserving telomere we could potentially prevent adverse effect of diabetes
Breast Cancer has a particular preference to form cancer metastases in bone where its presence is associated with bone destruction that frequently results in significant pain and disability. Bone seems to provide a fertile soil for breast cancer cells that have moved into the blood vessels from the original cancer site in the breast. Once tumour cells have invade bone marrow spaces from the blood vessels they are able to grow and induce the normal cells of the bone marrow to destroy the surround ....Breast Cancer has a particular preference to form cancer metastases in bone where its presence is associated with bone destruction that frequently results in significant pain and disability. Bone seems to provide a fertile soil for breast cancer cells that have moved into the blood vessels from the original cancer site in the breast. Once tumour cells have invade bone marrow spaces from the blood vessels they are able to grow and induce the normal cells of the bone marrow to destroy the surrounding hard bone. This allows the tumour to grow faster. Together these processed create a vicious cycle that contributes to the serious consequences of bone metastases. In this project we will be studying mice with breast cancer to understand what makes the bone marrow such a fertile and receptive site for breast cancer metastasis. In particular, we are looking at how the normal processes of bone renewal and repair contribute to the establishment of cancer in bone. We will use the body's own bone protecting protein, called osteoprotegerin, to test how blocking bone destruction will affect the ability of cancer cells to invade and grow in bone. This study has the potential to change the way bone metastases are treated. Treatment of breast cancer could be significantly improved if the fertile soil of bone could be modified to either block the targeting of breast cancer to bone, or to inhibit its growth there.Read moreRead less
Dietary Protein Effects In Elderly Women: Musculoskeletal, Renal, Cardiovascular And Body Composition Endpoints
Funder
National Health and Medical Research Council
Funding Amount
$478,946.00
Summary
Fractures and falls of the elderly are major health problems in our community in terms of disability and cost. It is critical to the future health of our aging population to develop non-pharmaceutical interventions to maintain health into old age. Epidemiologic studies have shown that relatively high protein intake is associated with increased bone mineral mass and reduced incidence of osteoporotic fracture in elderly people. Low protein intakes can lead to loss of muscle mass. To date there hav ....Fractures and falls of the elderly are major health problems in our community in terms of disability and cost. It is critical to the future health of our aging population to develop non-pharmaceutical interventions to maintain health into old age. Epidemiologic studies have shown that relatively high protein intake is associated with increased bone mineral mass and reduced incidence of osteoporotic fracture in elderly people. Low protein intakes can lead to loss of muscle mass. To date there have been no randomised trials of sufficient duration to examine the effects of increased dietary protein intake on bone and muscle health of the elderly. The aim of this study is to examine the effectiveness of protein supplementation for the prevention of osteoporosis and muscle wasting in elderly women, and the safety of such an intervention through monitoring renal function and risk factors for cardiovascular disease. Two hundred and twenty women will be recruited to this study and be assigned to protein group or placebo group. Women in the protein group will received 250 ml high protein drink (containing 30 g protein) per day and women in the placebo group will receive placebo drink containing the same amount of energy, calcium but no additional protein. Bone structure, muscle mass, body composition, renal function and risk factors for cardiovascular disease will be monitored during the 2 year study period. The results of this randomised, controlled study will clarify the role of protein on bone mass and structure, muscle mass and body composition in the elderly. At the same time, the safety of such intervention on renal and cardiovascular endpoints will also be evaluated. It is envisaged that the results of this study if positive will translate into both immediately applicable intervention strategies that are relevant at a program and an individual level.Read moreRead less
The Role Of Urotensin II In Diabetes-Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$405,594.00
Summary
People with diabetes most commonly die from stroke or heart attack and we need to determine what makes them more prone to these problems. The recently discovered UII system is increased in people with diabetes and has been found in diseased parts of blood vessels. Thus, the aim of this project is to characterise the UII system in the setting of diabetes using 2 unique genetically altered mice and a blocker a to study the effects of high cholesterol, diabetes and a deletion of UII.
Type 2 diabetes is caused by multiple genetic defects, resulting in high blood sugar levels. These high sugar levels are primarily due to a decrease in the concentration of insulin, a hormone produced by the pancreas. A number of recent studies have aimed to identify which genes are regulated under conditions that mimic diabetes. One gene shown to have altered expression levels under these conditions is an enzyme called fructose-1,6-bisphosphatase (or FBPase). This enzyme is involved in the meta ....Type 2 diabetes is caused by multiple genetic defects, resulting in high blood sugar levels. These high sugar levels are primarily due to a decrease in the concentration of insulin, a hormone produced by the pancreas. A number of recent studies have aimed to identify which genes are regulated under conditions that mimic diabetes. One gene shown to have altered expression levels under these conditions is an enzyme called fructose-1,6-bisphosphatase (or FBPase). This enzyme is involved in the metabolism of sugar and is usually expressed at undetectable levels in the pancreas, but when blood sugar levels are high, the amount of FBPase in the pancreas increases considerably. We hypothesise that this increase in FBPase may contribute to the decrease in insulin secretion by the pancreas, seen in the diabetic state. The aim of this proposal therefore is to study mice that we have modified to express increased FBPase specifically in the pancreas, in order to determine whether this will lead to a decrease in insulin release and to diabetes. If this is the case, then FBPase could be targeted for the development of drugs that would improve the control of blood sugar levels in diabetes.Read moreRead less
Effects Of Replacement And Withdrawal Of Testosterone In Human Males On Muscle, Bone And Fat
Funder
National Health and Medical Research Council
Funding Amount
$156,682.00
Summary
Male sex hormone or androgen deficiency (AD) is a common, but under-diagnosed condition. AD decreases well being and contributes to muscle weakness, bone fragility and weight gain. Cutting edge technology will be used to help explain how AD may relate to these negative effects, particularly on muscle function. Given the importance of aging, frailty, osteoporosis and obesity, understanding the role of hormones in these conditions may have major implications for prevention and treatment.
Nutrient And Hormone Delivery To Muscle: Interactions Between Insulin And Exercise
Funder
National Health and Medical Research Council
Funding Amount
$304,375.00
Summary
Exercise is known to be beneficial in the treatment and prevention of Type 2 diabetes and in particular muscle insulin resistance. Also, exercise and insulin share similar acute actions on muscle. Firstly, muscle contraction has a well established action to increase glucose uptake, and secondly, both muscle contraction and insulin act to increase capillary recruitment. This latter phenomenon is thought to enhance nutrient delivery and waste product removal. There is evidence that the increase in ....Exercise is known to be beneficial in the treatment and prevention of Type 2 diabetes and in particular muscle insulin resistance. Also, exercise and insulin share similar acute actions on muscle. Firstly, muscle contraction has a well established action to increase glucose uptake, and secondly, both muscle contraction and insulin act to increase capillary recruitment. This latter phenomenon is thought to enhance nutrient delivery and waste product removal. There is evidence that the increase in capillary flow due to muscle contraction is accompanied by increases in total blood flow. For insulin action we now have preliminary data to indicate that capillary recruitment occurs within a 5-10 min application of a physiologic dose of insulin independent of a change in total blood flow suggesting a redistribution of flow. Muscle contraction also increases capillary recruitment and it raises the question of whether similar mechanisms underlie insulin- and muscle contraction-induced capillary recruitment or whether there are distinct and complementary pathways. In this project we plan to define the mechanisms responsible for contraction- and insulin-induced capillary recruitment in muscle. We hypothesize that similar mechanisms are operative, with both insulin and muscle contractions acting via NO-dependent mechanisms. Because of capillary reserve, and different initial steps of the signalling systems stimulated by insulin and exercise, capillary recruitment by combined contraction and insulin stimuli will be additive at both sub maximal and perhaps at maximal insulin pathway stimulation. Signalling mechanisms will be compared and the role of non-nutritive route as a flow reserve assessed.Read moreRead less