The amyloid beta (Ab) protein is implicated in Alzheimer’s Disease through its ability to impair brain metabolism. We have recently found that Ab can also impair metabolism in other tissues. This project will determine the role of Ab in regulating whole body metabolism and determine whether it is implicated in the development of metabolic diseases such as type 2 diabetes.
Understanding The Metabolic Consequences Of Impaired AMPKa2 And NNOS� In Skeletal Muscle: Implications For The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$575,527.00
Summary
The inability of muscle to utilise sugar from the blood is a major problem that contributes to obesity and Type 2 diabetes. Since the number of people with these diseases will at least double by 2030, we need to find out what causes this problem. We will examine whether two muscle proteins that are impaired in obesity and Type 2 diabetes are also responsible for impaired sugar utilisation. We think that increasing these muscle proteins will fix the _sugar problem�, and remedy these diseases.
Sphingosine Kinase: A Target For Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$626,845.00
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 liver 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 liver.
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.
Blocking IL-6 Trans-signaling: A Therapeutic Strategy To Prevent Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$540,636.00
Summary
It is well known that blocking the recruitment of specific immune cells namely macrophages to adipose tissue of obese patients will improve their metabolic health. However, to date, a viable drug to do this has remained elusive. We have developed such a drug called sgp130Fc. This project will test the effectiveness of this drug in a pre-clinical setting.
How Does Paternal Obesity Influence Offspring Glucose Tolerance?
Funder
National Health and Medical Research Council
Funding Amount
$503,398.00
Summary
Obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. We have shown that normal females mated with obese fathers consuming high fat diet, produce offspring who develop glucose intolerance and impaired insulin secretion. This work will examine the mechanisms underlying this effect in the rat, testing a novel role for environmental factors in the father on disease in offspring that may be relevant to the growing obesity epidemic.
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.
Activation Of HSP72 In Skeletal Muscle As A Therapeutic Target For Obesity
Funder
National Health and Medical Research Council
Funding Amount
$656,033.00
Summary
We recently discovered that activation of a protein, namely Heat Shock Protein 72, can prevent obesity and insulin resistance in mice. We have developed a small molecule activator of this protein which has undergone preliminary human clinical trials. This project will extend upon this initial finding to determine the precise mechanism by which activation of this protein prevents obesity and insulin resistance.
It’s The Amount That Counts: The Impact Of Seven Days Of Sleep Restriction On Predictors Of Type 2 Diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$743,269.00
Summary
The aim of this project is to examine the relationship between sleep duration (5, 6, 7, 8, or 9h per day for one week) and glucose metabolism. This will allow us to quantify the amount of harm that different levels of sleep loss cause to the physiological systems that protect people from developing serious health disorders. In particular, the results of the project will be invaluable in the design of effective behavioural interventions for the prevention and/or treatment of type 2 diabetes.
Defining Factors That Contribute To Individual Diversity In The Diet-health Axis
Funder
National Health and Medical Research Council
Funding Amount
$1,668,059.00
Summary
There is a complex interplay between nutrition and genetics such that one diet maybe good for some but not for others depending on genetic makeup. Preliminary experiments in flies and mice support this. We found that for some flies, diets high in fat are harmful resulting in short life but certain flies resist the harmful effects of fat and live a longer lives. We propose to unravel the gene-environment interaction and determine which genes might lead to optimal health outcomes on certain diets.