Regulation Of Insulin Sensitivity By Reactive Oxygen Species
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
In morbid obesity and type 2 diabetes chronic levels of reactive oxygen species (ROS) are detrimental and diminish insulin's ability to maintain normal blood glucose levels. Paradoxically, ROS also promote insulin action by inhibiting enzymes known as protein tyrosine phosphatases (PTPs). This proposal will determine whether the promotion of ROS for the inhibition of PTPs early in the progression of type 2 diabetes may be of therapeutic benefit.
The prevalence of type 2 diabetes in increasing worldwide, the International Diabetes Federation predicting 435 million will have diabetes in 2030. The major driver of the diabetes epidemic is obesity. There is strong evidence linking type 2 diabetes and obesity to an increased risk of cancer. However, the exact mechanism promoting cancer development in obese and diabetic individuals is not clear. This project will examine the effects of high insulin levels on cancer development and progression.
Molecular Determinants Of Advanced Disease In Ovarian Granulosa Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$612,244.00
Summary
Granulosa cell tumours of the ovary (GCT) represent 5-10% of malignant ovarian cancers. They are distinct from the more common epithelial tumours and although considered to have a much better prognosis, they have a propensity to late recurrence. Recurrent or aggressive GCT have a poor prognosis. These studies will investigate the molecular basis of recurrence and aggressive behaviour in GCT. This will provide both prognostic information and also potential therapeutic targets.
Cytokine Signalling And Insulin Resistance In Obesity.
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
Western communities are experiencing an epidemic of obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating why being overweight and obese causes diabetes. Improved understanding about how hormones regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines for the treatment of obesity and the prevention of diabetes.
Osteocytic SOCS3 Controls STAT3:STAT1 Balance And Bone Formation
Funder
National Health and Medical Research Council
Funding Amount
$648,164.00
Summary
The most promising new osteoporosis therapy is antibody-based inhibition of the sclerostin protein. We discovered that sclerostin is inhibited by oncostatin M (OSM) only when it binds to a receptor called LIFR, which then activates proteins STAT3 and SOCS3. If OSM binds a different receptor (OSMR) it increases STAT1 activity and destroys bone. This project will determine how to manipulate STAT3, SOCS3, and STAT1 to increase bone formation and provide new treatments for osteoporosis.