Sphingosine Kinase As A Target Therapeutic For Obesity Induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$450,390.00
Summary
Obesity is linked to the development of insulin resistance and diabetes, which represent a significant health issue in Australia. A number of factors contribute to the development of insulin resistance, including defective fatty acid metabolism. This study proposes to investigate whether manipulating sphingosine kinase, a key enzyme in lipid metabolism, affects the development of insulin resistance. These studies may identify novel targets for the treatment of insulin resistance and diabetes.
Role Of FoxO Proteins In The Regulation Of Skeletal Muscle Anabolism, Catabolism And Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$503,426.00
Summary
Loss of muscle tissue or muscle wasting is a hallmark of many common health problems including diabetes, cancer, Cushing's syndrome, sepsis, HIV-Aids and renal failure. In the past 2-3 years important progress has been made in understanding the molecular regulation of both catabolism (muscle wasting) and anabolism (muscle growth) within mammalian skeletal muscles. It has been known for some time that a certain family of transcription factors, known as FoxO proteins, activate catabolic pathways. ....Loss of muscle tissue or muscle wasting is a hallmark of many common health problems including diabetes, cancer, Cushing's syndrome, sepsis, HIV-Aids and renal failure. In the past 2-3 years important progress has been made in understanding the molecular regulation of both catabolism (muscle wasting) and anabolism (muscle growth) within mammalian skeletal muscles. It has been known for some time that a certain family of transcription factors, known as FoxO proteins, activate catabolic pathways. However, recently, we have shown that FoxO proteins also cause muscle wasting by blocking anabolic pathways. Our new data heighten the importance of targeting FoxO proteins are therapeutics for human diseases where muscle tissue wasting occurs. This proposal will investigate methods that will allow for blocking the action of FoxO proteins in the hope that muscle wasting can be prevented.Read moreRead less
Circulating Ceramides, Inflammation And Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$358,319.00
Summary
Ceramides are a type of fat that are stored in the body. When people store too many ceramides in their muscles and liver they no longer respond normally to insulin, which leads to the development of type 2 diabetes. Ceramide levels are increased in the blood of people with type 2 diabetes. The aim of the this project is to determine whether ceramides in the blood contribute to type 2 diabetes and whether reducing ceramide levels in the blood improves health.
Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
Adipose Triglyceride Lipase: Regulation And Implications For The Aetiology Of Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$323,453.00
Summary
Obese individuals have elevated fat levels in the blood and muscle, which contributes to the development of other diseases such as type 2 diabetes. A newly discovered protein named adipose triglyceride lipase (ATGL) is essential for fat breakdown. This project aims to identify how ATGL operates and determine whether defective ATGL function leads to type 2 diabetes. These studies will assist in the development of strategies aimed at reducing fatty acids in blood and muscle.
Identifying A Novel Role For Pigment Epithelium-derived Factor In Obesity-related Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$361,637.00
Summary
Obesity is an important factor contributing to insulin resistance and type 2 diabetes; however, the factors linking these disorders are not well defined. A protein called PEDF is elevated in obesity and type 2 diabetes. This project will examine how PEDF causes insulin resistance and whether blocking PEDF's actions prevents insulin resistance. Successful completion of this project may lead to therapeutics that reduce the risk of developing type 2 diabetes.