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.
Study Of The Functional Consequences Of Angiotensin II Induced Increases In Renal Innervation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely imperv ....Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely impervious to preventative public health measures. While treatment of established high blood pressure can reduce the incidence of cardiovascular disease, preventing the development of hypertension in the first place is not possible at this time. A major impediment to the development of effective public health measure is our lack of knowledge of the pathological mechanisms involved, despite over 100 years of active research effort. The experiments planned in this study will probe below the surface of two important facts known about hypertension but not previously brought together - that the kidney's blood vessels and nerves are remodeled in hypertension, and that the kidney's control of the level of blood pressure must be changed in order for high blood pressure to develop in the first place. We hope that pursuit of this experimental line of enquiry will provide new clues on where to look for initiating factors in human hypertension.Read moreRead less
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.