Type 2 diabetes is a health crisis in Australia. In this project, we will investigate the mechanisms whereby high glucose and fat impair pancreatic beta-cell function leading to type 2 diabetes. We will establish how endoplasmic reticulum stress and the protein Id1 are linked with loss of beta-cell gene expression and function. The information gained will further our understanding of the basic mechanisms regulating insulin secretion and provide new therapeutic targets for diabetes treatment.
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.
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.
Mechanisms Of Islet Graft Rejection And Acceptance
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
Islet grafts offer diabetic patients the promise of a return to insulin-independence. In this project we will study how natural regulatory T cells suppress islet graft rejection in a mouse model. We will determine where regulatory T cells interact with graft-rejecting T cells, and define the mechanisms used to mediate their suppressive effects. Our findings will aid in developing new ways to induce long-term acceptance of islet grafts without immunosuppressive drugs.