Defining the molecular and cellular mechanisms of beta cell dysfunction. This project will investigate the influence of environment in the functional adaptation and maladaptation of pancreatic beta cells in diabetes. The research will define the molecular and cellular mechanisms linking environmental triggers such as obesity, high fatty acid levels and hyperglycaemia to beta cell dedifferentiation and dysfunction.
Effect Of Testosterone Treatment Combined With Dietary Restriction On Body Fat Mass And Muscle Function In Obese Men: A Randomized Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Obesity, an increasing health and economic burden, is associated with lowered testosterone levels in men. While both dietary restriction and testosterone treatment reduce body fat, whether a combination of these two approaches achieves a more pronounced fat mass reduction is unknown. We will conduct a rigorous 12 month clinical trial of testosterone treatment in 150 obese men with a low testosterone level. All men will receive dietary intervention to induce and maintain weight loss
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.
In the last decade there has been a substantial increase in the number of overweight and obese individuals. Obesity is now a major public health issue in Australia and, along with its associated disorders of type 2 diabetes and heart disease, incurs significant health care costs. There is a widespread awareness of the problem, but it has proved difficult to bring this obesity epidemic under control, and unless we can understand the underlying causes, the trend seems set to continue. This researc ....In the last decade there has been a substantial increase in the number of overweight and obese individuals. Obesity is now a major public health issue in Australia and, along with its associated disorders of type 2 diabetes and heart disease, incurs significant health care costs. There is a widespread awareness of the problem, but it has proved difficult to bring this obesity epidemic under control, and unless we can understand the underlying causes, the trend seems set to continue. This research proposal seeks to define the mechanisms which lead to the development of obesity. Evidence from a large range of clinical and population-based studies has shown that infants who are exposed to an increased supply of nutrients before birth have an increased risk of being overweight or obese as children and adults. It is not however, fully understood why this occurs. In normal adults, factors released by fat cells play an important role in the maintenance of energy balance, and changes in the levels of these factors in the fat cell or in the circulation can lead to increased weight gain and the development of poor sensitivity of the body's tissues to the actions of hormones, such as insulin. Fat cells develop before birth, and therefore changes in nutrient supply to the fetus have the potential to alter the functional properties of fat cells for life. In this proposal, we will investigate the effect of being exposed to an increased supply of nutrients in fetal life on the properties of fat cells after birth and define how such changes explain the development of obesity in these individuals. Understanding the mechanisms which link the risk of obesity to events before birth will allow clinicians of the future to provide children who are born to overweight, glucose-intolerant or diabetic mothers with a healthy start to life.Read moreRead less
Osteoporosis is a common problem with increased premature mortality associated with hip and even more minor fractures. The cause of increased mortality is debated although osteoporosis treatment may decrease this risk. This study will be the first to examine survival of all subjects in NSW admitted for a fracture including cause for subsequent hospitalisation and treatment taken. This study will help define the cause of the mortality and the role of anti osteoporosis treatment on outcome.
Aromatase Regulation By P53 And HIF-1alpha In Obesity And Post-menopausal Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$607,523.00
Summary
Current hormone therapy for breast cancer using inhibitors of oestrogen production results in serious side-effects including bone loss, joint pain and possibly cognitive issues. Our current work is aimed at understanding how oestrogen production is regulated with the goal of developing breast-specific inhibitors of oestrogen production to obviate these problems. In addition, this work is aimed at devising therapeutic intervention to break the linkage between obesity and breast cancer.
Type 2 diabetes is a health crisis in Australia. In this project, we will investigate the mechanisms whereby high glucose and fat impair pancreatic beta-cell function leading to type 2 diabetes. We will establish how endoplasmic reticulum stress and the protein Id1 are linked with loss of beta-cell gene expression and function. The information gained will further our understanding of the basic mechanisms regulating insulin secretion and provide new therapeutic targets for diabetes treatment.
Brown fat protects animals against obesity and diabetes. Humans with abundant brown fat are metabolically healthy. Identification of medication that boosts brown fat function may lead to novel treatment of metabolic disorders. This proposal will examine the role of such a medication, which is modeled on a factor (called FGF21) released from brown fat. The project will also search for other factors released by human brown fat, which may become future targets of obesity treatment.
Reversal Of Diabetes In A Humanised Mouse Using A Clinically Applicable Vector System
Funder
National Health and Medical Research Council
Funding Amount
$842,173.00
Summary
Somatic gene therapy is one of the strategies that is being considered to cure Type I diabetes. Specifically, we wish to engineer liver cells to replace beta cell function. The aim of this project is to design a clinically-applicable protocol for the reversal of diabetes using a recombinant adeno-associated vector that delivers genes to human livers with high efficiency showing long term expression without pathogenicity and immunogenicity following a simple intra-peritoneal injection.