Developing Clinical Islet Transplantation For Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$387,337.00
Summary
This fellowship will provide me the opportunity to advance islet transplantation as a curative treatment for people with type 1 diabetes. The ultimate goal is to use cell-based therapy to achieve insulin independence for all people with type 1 diabetes. It aims to do this by developing a collaborative network between scientists and clinicians to advance human islet transplantation as a treatment for type 1 diabetes and to develop genetically engineered pig cells as a novel source of insulin prod ....This fellowship will provide me the opportunity to advance islet transplantation as a curative treatment for people with type 1 diabetes. The ultimate goal is to use cell-based therapy to achieve insulin independence for all people with type 1 diabetes. It aims to do this by developing a collaborative network between scientists and clinicians to advance human islet transplantation as a treatment for type 1 diabetes and to develop genetically engineered pig cells as a novel source of insulin producing cellsRead moreRead less
Beta Cell Mass In Type 1 Diabetes Mellitus And Islet Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$3,070,136.00
Summary
This research program will examine the cellular and molecular mechanisms underlying the loss of Beta cell mass and function: During the pathogenesis of Type 1 Diabetes Mellitus (T1D); and Following islet transplantation. Though these processes have traditionally been considered to be purely immune-mediated, it is now clear that the response of the beta cell is critical to the final outcome of the auto-immune process and response to therapeutic interventions. Thus the complex interactions between ....This research program will examine the cellular and molecular mechanisms underlying the loss of Beta cell mass and function: During the pathogenesis of Type 1 Diabetes Mellitus (T1D); and Following islet transplantation. Though these processes have traditionally been considered to be purely immune-mediated, it is now clear that the response of the beta cell is critical to the final outcome of the auto-immune process and response to therapeutic interventions. Thus the complex interactions between the cellular and soluble constituents of the immune system, plus the effects of a deregulated metabolic milieu, are integrated at the beta cell. This in turn activates a series of complex transcriptional programs in the beta cell that together determine the beta cells ultimate functional status and survival. We will use knowledge gained from studying these processes to drive the development of novel therapeutic targets and strategies to improve the success of immune-based and transplantation-based therapies.Read moreRead less
The Role Of Insulin Hypersecretion In Beta Cell Dysfunction In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$318,622.00
Summary
The treatment of diabetes involves the use of drugs that stimulate the release of insulin from the pancreas to reduce the high blood sugar levels. However, we believe that while in the short term this is a good strategy, in the long-term it damages the cells that produce insulin leading to a worsening state of diabetes. It is the aim of this application to understand the mechanisms by which the insulin producing cells are damaged when forced to oversecrete insulin.
Biochemical Basis Of Islet Beta-cell Compensation And Failure In Normal Pregnancy And Gestational Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$480,828.00
Summary
The factors causing the current world-wide crisis of rapidly rising diabetes prevalence remain poorly understood. Of potential major importance, however, is the hypothesis that abnormalities in the maternal metabolic environment, as occur in gestational diabetes (GDM) (diabetes that develops in pregnancy), result in abnormal development of metabolic systems in the baby resulting in higher risk of adult onset diabetes in the babies. Therefore, it is of importance to understand the mechanisms caus ....The factors causing the current world-wide crisis of rapidly rising diabetes prevalence remain poorly understood. Of potential major importance, however, is the hypothesis that abnormalities in the maternal metabolic environment, as occur in gestational diabetes (GDM) (diabetes that develops in pregnancy), result in abnormal development of metabolic systems in the baby resulting in higher risk of adult onset diabetes in the babies. Therefore, it is of importance to understand the mechanisms causing GDM, such that effective measures can be developed to counter this passing on of diabetes risk from mother to baby. It is known that a key factor causing GDM is failure of maternal pancreatic islet beta-cells to compensate for increased demands for insulin production in pregnancy. Poorly understood, however, are the cellular mechanisms of islet beta-cell compensation in normal pregnancy and failure of this compensation in GDM pregnancy. We have recently shown that there is a pathway of fat metabolism (triglyceride- free fatty acid cycle) within the islet beta-cell that has an important role in amplyfing insulin secretion necessary to maintain normal blood glucose and protecting the islets from failure in obese rats. The major focus of this project is to test the hypothesis that this pathway has a key role in the adaptation of pancreatic islets to normal pregnancy and its dysfunction contributes to the causation of GDM. Of great interest from preliminary findings is that a master regulator of glucose and fat metabolism, PGC1alpha, is markedly reduced in islets during normal pregnancy. Studies will also be directed to PGC1alpha's role in islet adaptation to pregnancy and failure in GDM. We expect that successful completion of this project will lead to the development of highly targeted counter measures to prevent GDM and to slow and reverse the current epidemic of diabetes.Read moreRead less
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.
At least 6 young Australians are diagnosed each day with type 1 diabetes. This Program aims to change the way type 1 diabetes is managed by proactively treating its underlying mechanisms. We will develop safer and more effective immune therapies, develop islet transplantation, look for better markers of disease, and identify ways to preserve insulin-producing cells. The Program aims to propel type 1 diabetes research forward to reach the goals of prevention and cure.
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.