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
Can Exercise Early After Spinal Cord Injury Prevent Deterioration Of Muscle And Bone?
Funder
National Health and Medical Research Council
Funding Amount
$775,049.00
Summary
Spinal cord injury leads to a profound deterioration of the muscles and bones in the paralysed limbs. This project will examine the effects of exercising the paralysed limbs as early as possible after injury to prevent muscle and bone loss rather than restoring the tissues once changes have occurred. The time course and mechanisms underlying the microstructural decay of bone over the first year after injury will also be examined to provide a basis for determining fracture risk in this group.
PREVention Of Diabetes Through Lifestyle Intervention And Population Studies In Europe And Around The World
Funder
National Health and Medical Research Council
Funding Amount
$345,281.00
Summary
The PREVIEW Study will identify the most efficient lifestyle pattern for the prevention of type-2 diabetes in a population of pre-diabetic overweight or obese individuals. The project comprises two distinct lines of evidence, an intervention study and population studies. The focus will be on diet (specifically protein and glycemic index) and intensity of physical activity, as well as their interaction with the lifestyle factors, habitual stress, sleeping pattern, behavioural, environmental, cult ....The PREVIEW Study will identify the most efficient lifestyle pattern for the prevention of type-2 diabetes in a population of pre-diabetic overweight or obese individuals. The project comprises two distinct lines of evidence, an intervention study and population studies. The focus will be on diet (specifically protein and glycemic index) and intensity of physical activity, as well as their interaction with the lifestyle factors, habitual stress, sleeping pattern, behavioural, environmental, cultural, and socioeconomic variables.Read moreRead less
Type 1 Diabetes And The Metabolic Syndrome: Defining This Modern-day Phenotype, And Exploring The Effects Of Exercise On Glycaemic Control And Both Traditional And Novel Diabetes Complications
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
This research aims to define trends in the prevalence of, and complications associated with, metabolic syndrome in adults with type 1 diabetes, using the Australian National Diabetes Information Audit and Benchmarking Initiative (ANDIAB). Subsequently, a randomised controlled trial will examine the effect of exercise on glycaemic control and diabetes complications risk profiles in this group. These studies will thus address disease profiles and a potential beneficial clinical intervention.
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