Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their ....Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their etiology, both forms result in an inability of the body to control blood sugar levels. Beta cells release the hormone insulin, which regulates blood sugar levels. Current knowledge suggests that a loss of beta cell mass is important for both diseases. For type I diabetes the beta cells are destroyed by the immune system. Though for type 2 diabetes the causes are less clear, it is apparent that the beta cells are dying. Our research is focused on understanding the molecular pathways that control beta cell survival and regulate their death. Such knowledge would help us understand the complex processes leading to the development of diabetes. Furthermore, we could use this knowledge in the design of genetic engineering strategies to create 'death-defying' beta cells, as a potential therapeutic strategy for the treatment of diabetes.Read moreRead less
Investigation Of A New Hypothesis That Increased TGF? Activity In Developing Fetal Organs Predisposes A Women To Polycystic Ovary Syndrome And Associated Metabolic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
Have you ever wondered why some people get fat and other do not, no matter how much they eat? The answer could lie in what happened before they were born. This project investigates a new hypothesis that was developed from discoveries on polycystic ovary syndrome. Women with this syndrome are at increased risk of becoming overweight and diabetic. If the hypotheses prove correct it might be possible to reduce the incidence of these metabolic disorders in the longer term.
Development Of Engineered Novel Growth Factors For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$410,439.00
Summary
Infertility comes at an enormous social and financial cost to Australian society. The aim of this proposal is to improve the success rate of an innovative technology that matures eggs in the laboratory and so eliminates the need for the hormones normally used in IVF. To achieve this a newly discovered egg-secreted protein first has to be produced in the laboratory.
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
New Molecular Mechanisms Of Islet Protection Against Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$673,259.00
Summary
Type 2 diabetes is an enormous health and economic burden. The mechanisms of ?-cell compensation for insulin resistance and of ?-cell failure in type 2 diabetes are unclear. This proposal will test the novel hypothesis that the adaptation of endoplasmic reticulum (ER) capacity mediates ?-cell compensation, and that the failure of ?-cell adaptation to ER stress causes diabetes. The studies will show that targeting ER capacity is an important novel strategy for type 2 diabetes therapy.