Investigation Of Pancreatic Insulin-secreting Cell Function And Survival
Funder
National Health and Medical Research Council
Funding Amount
$375,750.00
Summary
Diabetes remains a major health problem in Australia. Both type 1 and type 2 diabetes is eventually due to pancreatic insulin-producing beta-cell destruction, which is caused mainly by the cell death, so called 'apoptosis' or programmed suicide of the cells. Thus, attempting to protect beta-cells against death and rescue their insulin secretory function is emerging as a strategy for the treatment of diabetes. However, how the beta-cells undergo death and how to protect the cell death are still n ....Diabetes remains a major health problem in Australia. Both type 1 and type 2 diabetes is eventually due to pancreatic insulin-producing beta-cell destruction, which is caused mainly by the cell death, so called 'apoptosis' or programmed suicide of the cells. Thus, attempting to protect beta-cells against death and rescue their insulin secretory function is emerging as a strategy for the treatment of diabetes. However, how the beta-cells undergo death and how to protect the cell death are still not completely understood. We have recently discovered a new protein, named sphingosine kinase, that is a strong protector against cell death. We also found that this enzyme is involved in process of insulin secretion. Thus, this application seeks to establish a dual role of this enzyme in protecting beta-cells from death and promoting insulin secretion by the cells. This will ultimately allow us to create new therapeutic strategy to target this protein for the management of diabetes.Read moreRead less
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
Apoptotic Pathways In Pancreatic Beta Cells Leading To Type 1 Diabetes And Transplant Rejection
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
The destruction of insulin-producing beta cells in the pancreas by immune cells leads to the need for daily insulin injections in patients with type 1 diabetes. This project aims to understand how beta cells are destroyed. A knowledge of the process by which this occurs will indicate ways we can protect these cells. Our previous work has suggested strategies that may protect beta cells, and we aim to test these. Such protection may eventually allow beta cell replacement by transplantation.
Ceramide Metabolism And ER Stress In Fatty-acid Mediated Destruction Of Pancreatic Beta Cells
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
The underlying cause of Type 2 diabetes is the failure of pancreatic beta cells to secrete sufficient insulin to overcome the insulin resistance that is associated with obesity. Beta cell failre is associated with both defective insulin secretion and loss of beta cell mass. This proposal focuses on the cellular mechanisms and stress pathways whereby too much fatty acid promotes beta cell death.
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.