A PROGRAM OF TRANSLATIONAL CARDIOVASCULAR MEDICINE: IDENTIFYING NEW TARGETS FOR PREVENTION AND TREATMENT
Funder
National Health and Medical Research Council
Funding Amount
$13,050,773.00
Summary
Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide, despite signficant advances in treatment. Our team has an international reputation for developing innovative approaches for the treatment of patients with CVD. We will work collaboratively to improve outcomes for people suffering from hypertension, heart attack, heart failure & other serious forms of CVD.
Diabetes And Dementia: Studies With The Fremantle Diabetes Study Cohort.
Funder
National Health and Medical Research Council
Funding Amount
$315,509.00
Summary
Dementia is an extremely serious condition which affects a large proportion of the older population. Recent evidence has shown that diabetes, which is another common condition in the elderly, doubles the risk of an older person developing Alzheimer's disease and other forms of dementia. Why this happens is unknown but insulin therapy has been highlighted as a possible cause. As many older people are on insulin for their diabetes, it is extremely important to confirm or refute this finding. It se ....Dementia is an extremely serious condition which affects a large proportion of the older population. Recent evidence has shown that diabetes, which is another common condition in the elderly, doubles the risk of an older person developing Alzheimer's disease and other forms of dementia. Why this happens is unknown but insulin therapy has been highlighted as a possible cause. As many older people are on insulin for their diabetes, it is extremely important to confirm or refute this finding. It seems possible that insulin may not be the direct cause but that some other associated factor such as poor diabetes control, recurrent hypoglycaemic attacks or cerebrovascular disease causes dementia. On theoretical grounds, Alzheimer's disease may have a vascular basis. If Alzheimer's disease was, in part, caused by vascular disease then there is the potential to prevent cases of dementia developing by paying attention to the known risk factors for vascular disease such as hypertension. The Fremantle Diabetes Study is an ideal group of community living diabetic individuals in which we can study whether some or all of these factors cause Alzheimer's disease or dementia and gain insights into the potential for prevention.Read moreRead less
The Involvement Of Bone Cells In The Adverse Side-effects Associated With Therapeutic Glucocorticoid Use
Funder
National Health and Medical Research Council
Funding Amount
$290,032.00
Summary
Long-term use of cortisone (glucocorticoids) often leads to significant health problems such as diabetes and obesity. We have convincing preliminary data suggesting these side effects are, at least in part, mediated via bone cells. Inhibiting cortisone action in these cells, in mice treated with cortisone, results in a significant reduction of the negative side effects of this drug on fuel metabolism (eg glucose and lipid levels). The current aim is to investigate how this pathway is involved in ....Long-term use of cortisone (glucocorticoids) often leads to significant health problems such as diabetes and obesity. We have convincing preliminary data suggesting these side effects are, at least in part, mediated via bone cells. Inhibiting cortisone action in these cells, in mice treated with cortisone, results in a significant reduction of the negative side effects of this drug on fuel metabolism (eg glucose and lipid levels). The current aim is to investigate how this pathway is involved in cortisone-induced obesity and diabetes.Read moreRead less
Alterations In Secretion And Gene Expression In Pancreatic Beta Cells Exposed To Lipid.
Funder
National Health and Medical Research Council
Funding Amount
$425,250.00
Summary
The project is aimed at a better understanding of the way in which fats control gene expression in the pancreatic beta cells of the islets of Langerhans. Because changes in gene expression are to likely to explain why exposure of these cells to fat disrupts their ability to release insulin, identification of these genes could explain why only some obese people develop Type 2 diabetes.
Biochemical Basis Of Islet Beta-cell Compensation And Failure In Normal Pregnancy And Gestational Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$480,828.00
Summary
The factors causing the current world-wide crisis of rapidly rising diabetes prevalence remain poorly understood. Of potential major importance, however, is the hypothesis that abnormalities in the maternal metabolic environment, as occur in gestational diabetes (GDM) (diabetes that develops in pregnancy), result in abnormal development of metabolic systems in the baby resulting in higher risk of adult onset diabetes in the babies. Therefore, it is of importance to understand the mechanisms caus ....The factors causing the current world-wide crisis of rapidly rising diabetes prevalence remain poorly understood. Of potential major importance, however, is the hypothesis that abnormalities in the maternal metabolic environment, as occur in gestational diabetes (GDM) (diabetes that develops in pregnancy), result in abnormal development of metabolic systems in the baby resulting in higher risk of adult onset diabetes in the babies. Therefore, it is of importance to understand the mechanisms causing GDM, such that effective measures can be developed to counter this passing on of diabetes risk from mother to baby. It is known that a key factor causing GDM is failure of maternal pancreatic islet beta-cells to compensate for increased demands for insulin production in pregnancy. Poorly understood, however, are the cellular mechanisms of islet beta-cell compensation in normal pregnancy and failure of this compensation in GDM pregnancy. We have recently shown that there is a pathway of fat metabolism (triglyceride- free fatty acid cycle) within the islet beta-cell that has an important role in amplyfing insulin secretion necessary to maintain normal blood glucose and protecting the islets from failure in obese rats. The major focus of this project is to test the hypothesis that this pathway has a key role in the adaptation of pancreatic islets to normal pregnancy and its dysfunction contributes to the causation of GDM. Of great interest from preliminary findings is that a master regulator of glucose and fat metabolism, PGC1alpha, is markedly reduced in islets during normal pregnancy. Studies will also be directed to PGC1alpha's role in islet adaptation to pregnancy and failure in GDM. We expect that successful completion of this project will lead to the development of highly targeted counter measures to prevent GDM and to slow and reverse the current epidemic of diabetes.Read moreRead less