In patients predisposed to metabolic diseases, excessive fats get delivered to various tissues. About 10 to 15% are converted into sphingolipids, many of which have deleterious effects on tissue function. Blocking sphingolipid production prevents diabetes and most cardiovascular diseases in rodents. We seek to better understand these mechanisms and determine how the observations can be translated into new therapies and better clinical outcomes.
Regulation Of Pancreatic Beta-cell Number And Function By Adipocyte-released Hormones, Free Fatty Acids And Ghrelin.
Funder
National Health and Medical Research Council
Funding Amount
$256,500.00
Summary
The disease diabetes mellitus comprises a heterogeneous group of disorders all characterised by high blood glucose levels. Beta-cells in the pancreas, which secrete insulin, are central to the pathophysiology of the disease. Type 1 or insulin-dependent diabetes mellitus results from an absolute deficiency of insulin due to auto immunological destruction of the pancreatic beta cell, and accounts for 5-10% of total diabetes mellitus. In the more common type 2 or non-insulin-dependent diabetes mell ....The disease diabetes mellitus comprises a heterogeneous group of disorders all characterised by high blood glucose levels. Beta-cells in the pancreas, which secrete insulin, are central to the pathophysiology of the disease. Type 1 or insulin-dependent diabetes mellitus results from an absolute deficiency of insulin due to auto immunological destruction of the pancreatic beta cell, and accounts for 5-10% of total diabetes mellitus. In the more common type 2 or non-insulin-dependent diabetes mellitus, liver, muscle and fat cells are resistant to the action of insulin and compensatory mechanisms that are activated in the beta-cell to increase insulin secretion are not sufficient to maintain normal blood glucose levels. In Western countries including Australia, type 2 diabetes currently affects around 2% of the whole population and about 6% of adults (10% of over 60-y) and continues to grow at around 6% per annum. Type 2 diabetes often occurs in obese patients and a direct link between obesity and type 2 diabetes has been strongly suggested by research to date. It has also been found that a progressive loss of beta-cell function throughout the course of the disease results in the reduction of insulin secretion. The contribution of excessive fat tissue in obese patients to the progress of type 2 diabetes is not clear. Certain hormones from fat cells, metabolic regulatory hormone, and fatty acids have been demonstrated to influence the function of beta-cells in previous studies, including our own. We now aim to investigate in detail the effect of these on cultured beta-cells with molecular and cell biology techniques. We expect to identify a factor or factors which stimulate or inhibit the progress of beta-cell dysfunction, with the potential to identify therapeutic targets in the treatment of type 2 diabetes.Read moreRead less
Type 2 diabetes is reaching epidemic proportions across the world and is a huge burden in health care costs. We know it is a multifaceted disease with many symptoms, one of which is a reduction in insulin secretion. This proposal sets out to determine the mechanisms of insulin secretion from healthy tissue and what goes wrong in disease.
Secretion is an essential step in memory and learning, control of metabolism and reproduction and the functioning of most organs. Secretory dysfunction also underlies many diseases including type 2 diabetes. We plan experiments to test for a new model of control of insulin secretion.
Mechanistic Studies Of Medium-chain Fatty Acids In Metabolism And Obesity.
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
A major factor underpinning metabolic disorders such as obesity and diabetes is unlimited access to high-fat diets. However, not all lipids have detrimental effects on metabolic health. Diets rich in medium-chain fatty acids are associated with reduced adiposity and preserved insulin action. This project will examine the mechanisms that underlie the beneficial effects of MCFA, with focus on a novel MCFA-receptor (GPR84) as a potential therapeutic target in the treatment of metabolic disease.
Defining The Mechanisms That Control Exocytosis And Cell Signalling In Health And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
This research focuses on pathways regulating nervous communication and hormone release. It centres on proteins that regulate this process and on the function of specific endocrine cells in health and disease. It uses unique research tools developed in this laboratory enabling the study of mechanisms regulating cell signalling. Through this research I aim to identify how the cells in our body communicate with each other and how this relates to diseases such as type 2 diabetes.
Is The Role Of IL6 In Metabolism Dependent On Its Cellular Origin?
Funder
National Health and Medical Research Council
Funding Amount
$714,061.00
Summary
Interleukin-6 is a protein secreted from many cells in the body. For over 10 years, a great deal of research has been undertaken to determine if this protein is "good" or "bad" for patients suffering from type 2 diabetes. We have evidence that IL-6 is both good and bad depending upon which cell produces it. We intend to fully explore this notion. This is most important to clarify the confusion amongst the field and because drugs that target the IL-6 receptor complex are in clinical development f ....Interleukin-6 is a protein secreted from many cells in the body. For over 10 years, a great deal of research has been undertaken to determine if this protein is "good" or "bad" for patients suffering from type 2 diabetes. We have evidence that IL-6 is both good and bad depending upon which cell produces it. We intend to fully explore this notion. This is most important to clarify the confusion amongst the field and because drugs that target the IL-6 receptor complex are in clinical development for type 2 diabetes.Read moreRead less
Hormone Transport By Alpha-2-Macroglobulin: Novel Roles In Regulating Hormone Activity
Funder
National Health and Medical Research Council
Funding Amount
$602,857.00
Summary
Alpha-2-macroglobulin is a large protein in the blood known to bind and transport numerous hormones in the circulation. Our previous studies published in BLOOD (2009) and JBC (2013) have discovered an important role for this molecule in the transport and regulation of a peptide hormone. The studies proposed in this application have important implications for understanding new roles of alpha-2-macroglobulin in hormone binding and regulating the activity of hormones in disease states.
Investigating Follistatin-based Interventions For Long Term-protection Against Frailty Associated With Chronic Illness And Aging
Funder
National Health and Medical Research Council
Funding Amount
$987,169.00
Summary
Effective therapies are urgently needed to combat frailty arising from muscle wasting associated with chronic illness and aging. The proposed studies will investigate the prospects of developing novel short-term interventions that can confer long-term benefits for preventing and treating muscle wasting associated with chronic illness and advanced aging.