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.
Diabetes is a major health epidemic; and both type 1 and type 2 diabetes can lead to the development of diabetic complications - the major cause of morbidity and mortality from diabetes. Loss of islet function is a key factor in diabetes and my testable hypothesis is that islet inflammation contributes to this process. We will investigate how genes effect islet inflammation. New understanding could lead to biomarkers for determining who is susceptible & new treatment opportunities.
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.
Elucidating The Mechanism Of IL-2 Cytokine/antibody Mediated Transplantation Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Organ transplantation is a life-saving treatment for end-stage organ failure. However, patients must take immunosuppressive drugs to prevent rejection, a lifetime of which increases the risk of infection and cancer. An alternative to drugs is to manipulate the immune system from within. We discovered a way to boost the immune ‘regulators’ so that they stifle the graft-destroying response. We are optimising this approach with the aim of transplanting organs without long-term immunosuppression.
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.
Manipulating The Balance Of Effector And Regulatory T Cells To Promote Islet Xenograft Survival
Funder
National Health and Medical Research Council
Funding Amount
$1,542,601.00
Summary
Type 1 diabetes destroys the body’s insulin-producing cells (islets), resulting in high blood sugar levels and the prospect of devastating complications. Replacement of islets by transplantation is the only way to restore normal blood sugar control, but (i) is limited by the shortage of human donors and (ii) carries risks associated with anti-rejection drugs. This project aims to solve both problems by using humanized pigs as donors combined with a novel approach to inducing tolerance to the tra ....Type 1 diabetes destroys the body’s insulin-producing cells (islets), resulting in high blood sugar levels and the prospect of devastating complications. Replacement of islets by transplantation is the only way to restore normal blood sugar control, but (i) is limited by the shortage of human donors and (ii) carries risks associated with anti-rejection drugs. This project aims to solve both problems by using humanized pigs as donors combined with a novel approach to inducing tolerance to the transplanted islets.Read moreRead less