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The Role Of The Osteoblast In Mediating Glucocorticoid-Induced Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$825,254.00
Summary
Glucocorticoids (GC) exceed most other drugs in terms of numbers of patients treated and indications. Preventing or attenuating the deleterious effects of GC on fuel metabolism is therefore of great clinical significance. Our studies will create new knowledge regarding the mechanisms of GC-induced diabetes and osteoporosis, and will contribute to the development of new approaches that are essential to tackle the pressing medical problem of GC-induced disease.
GLUCOCORTICOID EFFECTS ON BONE: THE ROLE OF THE OSTEOBLAST
Funder
National Health and Medical Research Council
Funding Amount
$464,520.00
Summary
Glucocorticoids (usually referred to as cortisone) are used as therapeutic agents in almost all fields of medicine, where they have been proven to be of great benefit to countless patients suffering from diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and malignancies. Glucocorticoids are also of live saving benefit to patients who have undergone organ transplantation. It is, however, well known that glucocorticoids may also exert deleterious effects on bone, muscle, ca ....Glucocorticoids (usually referred to as cortisone) are used as therapeutic agents in almost all fields of medicine, where they have been proven to be of great benefit to countless patients suffering from diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and malignancies. Glucocorticoids are also of live saving benefit to patients who have undergone organ transplantation. It is, however, well known that glucocorticoids may also exert deleterious effects on bone, muscle, cartilage and skin, causing osteoporosis, muscle wasting and skin damage. As a matter of fact, cortisone-induced muscle and bone disease is one of the most frequent and serious side effects associated with glucocorticoid treatment, and substantially affects quality of life and co-morbidity in many patients. In the present project, we aim to develop new strategies for the understanding and prevention of costisone-induced bone disease. The first step is to investigate the mechanisms of actions of glucocorticoids in bone. To this aim, we have generated a model in which a cortisone- inactivating enzyme is produced in excess in the bone forming cells (osteoblasts). Previous studies have shown that these cells are protected against the effects on cortisone, while other cells not producing this enzyme remained vulnerable. We now intend to use this model to study the mechanisms of glucocorticoid action on bone and muscle under normal and diseased conditions (e.g. in a model of glucocorticoid excess and in a model of rheumatoid arthritis). We also intend to study how internal glucocorticoids affect the development of bone forming cells. Our long-term aim is to uncover new ways to target drug action to the desired tissues and cells, while protecting other tissues and cells from deleterious side effects.Read moreRead less
Diabetic cardiomyopathy (DiabCM) is common in people with diabetes. It predisposes to heat failure. Its cause remains unclear and there is no specific treatment for DiabCM. Inflammation is a fundamental tissue response to a metabolic insult and it occur in DiabCM. The central hypothesis in this work is that inflammation through myocardial macrophage cells contributes to DiabCM. This hypothesis will be tested in animal models and also in cell culutre studies.
Biomarkers For Risk And Outcomes Of Type 2 Diabetes: A Discovery And Validation Approach In Australian And Chinese Subjects
Funder
National Health and Medical Research Council
Funding Amount
$599,489.00
Summary
The aim is to make better outcomes for people with Type 2 diabetes in Australia and China, by exploring various tests to improve prediction of diabetes progression, complication risk and treatment response. The team has data and samples from the Fenofibrate Intervention and Event Lowering in Diabetes Trial and from the Shanghai Diabetes Study. This approach is very time and cost-effective. We will also study animal models to understand mechanisms of diabetes damage, and test new treatments.
Analysis Of Effect Of Different Treatment Targets On Maternal And Child Health Outcomes In Gestational Diabetes Mellitus (GDM), Review Of Specific Treatments And Development Of Clinical And Biochemical Predictors.
Funder
National Health and Medical Research Council
Funding Amount
$122,686.00
Summary
This research aims to analyse newly proposed treatment targets for Gestational Diabetes Mellitus (GDM) and the effect this will have on maternal and child health outcomes, via comparison of data from two large Australian health services using the traditional and newly proposed critiera. The research will also investigate current effective interventions for GDM, including the impact of early antenatal lifestyle interventions, and formulation of a clinical and biochemical risk prediction model.
Can Vitamin D Prevent Diabetes By Improving Insulin Sensitivity And Secreation In Overweight Humans?
Funder
National Health and Medical Research Council
Funding Amount
$715,371.00
Summary
Vitamin D is mainly produced by the action of sunlight on skin. Low levels of vitamin D are becoming more common, as we work more indoors and avoid the sun and have been associated with type 2 diabetes. In proposed study, healthy overweight people, with low vitamin D, will be given vitamin D for 16 weeks to optimise blood levels of this vitamin. We will examine the changes in sugar metabolism. This study should provide important evidence on how vitamin D protects against diabetes and will suppor ....Vitamin D is mainly produced by the action of sunlight on skin. Low levels of vitamin D are becoming more common, as we work more indoors and avoid the sun and have been associated with type 2 diabetes. In proposed study, healthy overweight people, with low vitamin D, will be given vitamin D for 16 weeks to optimise blood levels of this vitamin. We will examine the changes in sugar metabolism. This study should provide important evidence on how vitamin D protects against diabetes and will support novel approaches to diabetes prevention.Read moreRead less
Cytokine Signalling And Insulin Resistance In Obesity.
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
Western communities are experiencing an epidemic of obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating why being overweight and obese causes diabetes. Improved understanding about how hormones regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines for the treatment of obesity and the prevention of diabetes.
Dietary Fats As Drivers Of Obesity-related Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Obesity leads to diabetes and heart disease but not all body fat seems to be bad. Increased fat around the waist (especially the visceral fat around the intestine and internal organs) is particularly bad. Visceral fat secretes a lot of inflammatory molecules. This research aims to understand how visceral fat becomes inflamed and how we might use diet and other methods to reduce both the amount of visceral fat and its level of inflammation; thus reducing both obesity and its health consequences.
Interactions Between Vasoactive, Epigenetic And Immunogenic Pathways In The Development Of Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
In our community, diabetic retinopathy is the leading cause of vision loss in people of working age. As the prevalence of diabetic retinopathy increases, there is an urgent need to understand the factors that cause its development in order to develop new treatments. This proposal will explore the contribution of hormones, the memory of retinal cells to high glucose and stress, and the immune system to diabetic retinopathy. The goal is to develop new and improved treatments for Australians.