The CDP Ethanolamine Pathway: A New Player In Obesity Induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$652,372.00
Summary
Insulin resistance, a characteristic of type 2 diabetes, is linked to abnormal metabolism of lipid (fat) in tissues such as liver and muscle. This project aims to identify a novel pathway which may promote a build up of lipids in muscle and therefore leads to the development of type 2 diabetes. This work may provide a basis for understanding and optimizing treatment of insulin resistance by regulating the control of fat metabolism in muscle.
Regulation Of Skeletal Muscle AMP-activated Protein Kinase By Glycogen
Funder
National Health and Medical Research Council
Funding Amount
$561,558.00
Summary
The enzyme AMP protein kinase has three parts (subunits) and is central to controlling the body's metabolism. We have discovered that one subunit is essential for tightly associating the enzyme with muscle glycogen which is a source of high energy and efficient metabolism. We will identify where the enzyme attaches to glycogen, and how diet and exercise alter this association. Understanding this could lead to new approaches for treating Type 2 diabetes where energy metabolism is disrupted.
An Integrated Approach To Identify The Molecular Mechanisms Contributing To The Pathogenesis Of Insulin Resistance: Targeting The Liver And Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
The inability of muscle and liver to utilise sugar from the blood is a major problem that contributes to the development of obesity and diabetes. How these problems occur is unknown. The goal of my research is to identify what causes the muscle and liver problem, and whether fixing these problems will reduce obesity and diabetes. Since the number of people with obesity and diabetes is predicted to double over the next decade, we need to understand the cause of these diseases.
Curing Fatty Muscles: Understanding The Role Of PLIN5 In Lipid Metabolism And Tissue Function
Funder
National Health and Medical Research Council
Funding Amount
$462,162.00
Summary
Diseases associated with the deposition of lipids in muscle are becoming an increasingly important medical problem as the incidence of obesity increases. Skeletal muscle and cardiac function are greatly altered by excessive lipid deposition. The protein PLIN5 is important in regulating fat metabolism. This project aims to determine the functions of PLIN5, how PLIN5 is regulated and whether altering PLIN5 contributes to the development of diabetes and heart failure.
An Essential Role For Skeletal Muscle FoxO1 In Protecting Against Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Skeletal muscle is the largest organ in the human body and accounts for approximately 80% of glucose disposal after a meal. We have identified a transcription factor, namely FoxO1, that appears protect against obesity-induced insulin resistance by promoting energy consumption. This project will examine whether skeletal muscle specific activation of FoxO1 is a possible therapeutic target for the treatment of obesity-induced insulin resistance.
REGULATION OF LIPID METABOLISM IN SKELETAL MUSCLE BY IDOL – A Novel Degrader Of The Very Low Density Lipoprotein Receptor
Funder
National Health and Medical Research Council
Funding Amount
$557,162.00
Summary
More than 1 in 5 Australians are estimated to have increased levels of fats (triglycerides; TGs) in the blood, commonly due to excess dietary intake or genetics. The excess TGs are deposited in skeletal muscle where they can cause insulin resistance, increasing the risk of developing diabetes, the fastest growing chronic condition in Australia. I will examine whether a recently identified protein, IDOL, can reduce accumulation of TGs in skeletal muscle and protect against insulin resistance.
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.
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.