The Role Of Endoplasmic Reticulum (ER) Stress In Pancreatic Beta-cell Dysfunction.
Funder
National Health and Medical Research Council
Funding Amount
$85,775.00
Summary
Diabetes results from pancreatic ß-cell failure which is characterised by insulin secretory defects and ß-cell destruction. This is mediated by inflammatory cytokines in type 1 diabetes and by high levels of fat in type 2 diabetes. The mechanisms by which ß-cells fail remain to be clarified but they are important considering the current epidemic of diabetes in Australia. This project will enhance our understanding of ß-cell failure and may provide therapeutic targets for diabetes treatment.
Endothelial And Mesenchymal Cell Interactions In Pancreatic Beta Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$95,583.00
Summary
Type 1 diabetes is a condition that arises when the body's immune system destroys insulin-producing beta cells within the pancreas. Recent studies have shown that normal glucose control can be restored by replacing the missing beta cells by transplantation of cells from deceased donors. However, the demand for transplant material outweighs supply. The work described in this application seeks to define how insulin-producing beta cells can be derived in the laboratory from embryonic stem cells.
Metabolically Reprogramming The Stroma To Starve Pancreatic Tumours
Funder
National Health and Medical Research Council
Funding Amount
$598,848.00
Summary
Pancreatic cancer claims five Australian lives every day. Despite aggressive treatment regimes, there has been no improvement in patient survival in the last decade. Evidence suggests that targeting cancer cells alone is not enough. Pancreatic tumours are surrounded by an extensive scar tissue reaction (stroma). This intense stromal reaction inhibits drug delivery and increases tumour growth. Thus, decreasing the stroma is a potential therapeutic strategy and is the focus of this proposal.
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.
Effects Of RHDL On Diabetes In TRAIL-deficient Mice.
Funder
National Health and Medical Research Council
Funding Amount
$294,892.00
Summary
Diabetes is a chronic disease affecting 275 people daily in Australia. People with diabetes have a 2-4 fold greater risk for developing cardiovascular disease (CVD). TRAIL (TNF-related apoptosis-inducing ligand) can promote cell growth and death selectively. High density lipoproteins are shown to protect against diabetes and CVD. Understanding the mechanism(s) that mediate this process may lead to the design of therapeutic agents to reduce suffering of patients with diabetes and CVD.
Role Of The Adaptive Unfolded Protein Response In Beta-cell Compensation
Funder
National Health and Medical Research Council
Funding Amount
$581,715.00
Summary
Obesity is a strong risk factor for type 2 diabetes. Obese subjects with “robust” pancreatic beta-cells can sustain a compensatory response. Type 2 diabetes arises in subjects with beta-cells that are “susceptible” to dysfunction and death. We will investigate the role of the adaptive unfolded protein response in beta-cell compensation for obesity-associated insulin resistance. Findings will help explain why some individuals but not others develop type 2 diabetes.
Role Of Lysosomal Acid Lipase In Regulating Insulin Secretion
Funder
National Health and Medical Research Council
Funding Amount
$570,928.00
Summary
Type 2 diabetes (T2D) affects 7% of Australians and is a major cause of morbidity and mortality. A failure of insulin secretion contributes to T2D, and this is linked to the inability of insulin producing ?-cells to use lipids appropriately (lipotoxicity). Here we will study the role of a cellular body called the lysosome to regulate ?-cell lipid metabolism and insulin secretion. This work will greatly increase the understanding of ?-cell failure in T2D.