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.
Stimulant laxatives are widely used and usually very effective in the short term, but how they work is very poorly understood. Our recent work has shown that they selectively excite sensory pathways from the colon which then trigger defaecation. This points to an undiscovered mechanism that potently affects colonic sensation and motility. This is likely to be a target for new treatments for other colonic disorders such as Irritable bowel syndrome and faecal incontinence.
Obstructive sleep apnea (OSA) is one of the most common complications of obesity and is independently associated with a reduced quality of life and cardiovascular disease. This project aims to identify the underlying factors linking obesity with OSA by examining how weight loss surgery can improve these factors. These important findings will contribute greatly to our understanding of OSA pathophysiology and are necessary to find better treatments for obesity-associated OSA.
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.
Combined Therapy To Ameliorate Ventilatory Instability In Patients With Heart Failure And Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$386,648.00
Summary
Sleep apnea is highly prevalent, particularly in patients with heart failure, and treatment remains limited to applying pressure via a face mask which can be intolerable. Although instability in breathing control is a major cause of apnea in many patients, treatments targeting instability with sufficient efficacy are unavailable. This project will combine two treatments, acetazolamide and oxygen, to powerfully reduce instability and provide relief from sleep apnea in a subgroup of patients.
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.