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.
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.
Mechanisms Responsible For Pancreatic Beta Cell Death And Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Diabetes is the fastest growing chronic disease both in Australia and worldwide. Current treatments are lacking effectiveness. Therefore, there is an urgent need to revolutionise diabetes therapy. Diabetes is caused by the failure of cells within the pancreas to produce sufficient insulin, resulting in uncontrolled blood sugar levels. This research proposal aims to investigate the processes and factors leading to this phenomenon in order to develop new strategies to overcome them.
Control Of Insulin Secretion By Y1 Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$675,582.00
Summary
Diabetes is the most common metabolic disease worldwide. Impaired insulin secretion and beta cell function is one of its major causes. We have recently discovered a key signaling pathway that we believe hold the secret to inhibiting insulin secretion in beta cells and blocking it leads to significant insulin release. This proposal focuses on this pathway and its regulation using innovative and unique tools. This will provide a novel treatment option for diabetes as well as islet transplantation.