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.
The Ghrelin Axis As A Target For Prostate Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$585,497.00
Summary
Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that ....Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that reduce quality of life for patients.Read moreRead less
HEREDITARY ENDOCRINE CANCER: A MODEL BASED ON PHAEOCHROMOCYTOMA- PARAGANGLIOMA SYNDROMES
Funder
National Health and Medical Research Council
Funding Amount
$875,894.00
Summary
Phaeochromocytomas and paragangliomas are tumours remarkable for their very high heritability. They have a high burden of disease themselves, and their associated hereditary syndromes include risks for other malignancies. Our study will rationalize the pathological approach to diagnosing these hereditary syndromes, find new therapeutic targets for metastatic disease, and provide a template for other cancers with high heritable component.
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.
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.
The proposal focuses on a novel angle explaining how pancreatic beta cells normally match their insulin synthesis, storage and secretion in response to an enhanced demand as occurs during obesity, and how this fails in the progression to Type 2 diabetes. In particular we will expand our discovery that glucose rapidly enhances the synthesis of a novel factor regulating gene transcription. This will generate basic knowledge that will potentially help design of novel therapies for Type 2 diabetes.
Role Of Macrophages In Lipotoxic Beta Cell Failure
Funder
National Health and Medical Research Council
Funding Amount
$612,736.00
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 the immune system and how this inhibits insulin secretion in T2D
Regulation Of Hypothalamic Insulin & Leptin Signalling By TCPTP
Funder
National Health and Medical Research Council
Funding Amount
$758,504.00
Summary
Insulin & leptin signal in the brain to lower blood glucose, suppress food intake, increase activity & increase energy expenditure. Obesity diminishes the abilities of insulin & leptin to signal. This proposal will determine if the enzyme TCPTP terminates insulin & leptin signaling in the brain. Our studies will provide insight into the molecular causes of obesity & may identify a novel therapeutic target for the treatment of obesity & type 2 diabetes.
Roles Of The Nuclear Growth Hormone Receptor In Cell Proliferation And Survival
Funder
National Health and Medical Research Council
Funding Amount
$429,387.00
Summary
We have discovered that the cell surface receptor for growth hormone travels to the cell nucleus in dividing cells, including cancer cells. Given the role of growth hormone in promoting growth postnatally, we seek to uncover how the nuclear receptor promotes proliferation directly, and by gene splicing. We have identified strong candidates for its direct actions through proteomics, and a DNA binding site for the receptor. Here we will investigate its role in proliferation, gene splicing and DNA ....We have discovered that the cell surface receptor for growth hormone travels to the cell nucleus in dividing cells, including cancer cells. Given the role of growth hormone in promoting growth postnatally, we seek to uncover how the nuclear receptor promotes proliferation directly, and by gene splicing. We have identified strong candidates for its direct actions through proteomics, and a DNA binding site for the receptor. Here we will investigate its role in proliferation, gene splicing and DNA strand break repair after cell irradiation.Read moreRead less