Investigation Of Novel Triterpenoids As New Potent AMPK Activators For The Treatment Of Insulin Resistant States
Funder
National Health and Medical Research Council
Funding Amount
$574,075.00
Summary
Type 2 Diabetes has major economic and health implications. Current medications are inadequate or have serious adverse effects. Triterpenoids have been used in traditional medicines for various diseases. This project builds on our recent discovery of novel triterpenoids with antidiabetic properties to investigate their efficacy and mechanisms of action. The results will provide valuable information about this class of molecules as potential new therapeutics for Type 2 diabetes.
Adiponectin: Key Factors Determining Its Metabolic Actions And Influences On Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$604,793.00
Summary
Diabetes and obesity are growing at alarming rates due to poor lifestyle and other factors. Adiponectin is a complex molecule secreted by fat tissue that may help to burn fat in other tissues such as muscle and liver. We investigate what are the main determinants of adiponectin action and how these might counteract defective insulin action caused by excessive fat intake. This promises to provide new therapeutic targets to lessen the metabolic derangement associated with diabetes and obesity
Phosphoproteomics: Metabolic And Exercise Signalling Markers For Sedentary And Trained Individuals
Funder
National Health and Medical Research Council
Funding Amount
$1,222,500.00
Summary
It is widely recognized that diet and exercise have a major influence on the health and fitness. Sedentary lifestyles predispose people to obesity and the early development of age onset diseases. In the past decade we have gained considerable insight into the regulatory links between exercise and metabolism particularly involving the AMPK signalling pathway. This project is concerned with the phosphoproteome of trained and untrained skeletal muscle, fat and erythrocytes as a marker of fitness.
Regulation Of Protein Kinases And Their Substrates
Funder
National Health and Medical Research Council
Funding Amount
$553,197.00
Summary
Our research is concerned with the control of the body's energy metabolism via an enzyme called AMPK. This enzyme is at the hub of metabolic control in response to diet and exercise. AMPK controls energy expenditure in response to demand as well as appetite. It is well recognized that diet and sedentary life-styles are major contributors to obesity and cardiovascular disease. We are testing how a new drug activates AMPKand how energy expenditure can be increased.
IS NITRIC OXIDE A CENTRAL REGULATOR OF EXERCISE-INDUCED SKELETAL MUSCLE MITOCHONDRIAL BIOGENESIS?
Funder
National Health and Medical Research Council
Funding Amount
$340,750.00
Summary
Mitochondria are the energy producing parts of the cell and are the major controllers of metabolism. There is now good evidence that reduced muscle mitochondrial size contributes to diabetes. Exercise is good for diabetics due partly to increasing muscle mitochondrial production (mitochondrial biogenesis). Unfortunately, little is known about the mechanisms involved in increased muscle mitochondrial biogenesis following exercise. It has been shown recently that nitric oxide (NO), a gas made by m ....Mitochondria are the energy producing parts of the cell and are the major controllers of metabolism. There is now good evidence that reduced muscle mitochondrial size contributes to diabetes. Exercise is good for diabetics due partly to increasing muscle mitochondrial production (mitochondrial biogenesis). Unfortunately, little is known about the mechanisms involved in increased muscle mitochondrial biogenesis following exercise. It has been shown recently that nitric oxide (NO), a gas made by muscle during exercise, plays a role in mitochondrial biogenesis in fat cells. This project will determine whether NO is a central regulator of exercise-induced mitochondrial biogenesis in skeletal muscle. If we find that NO increases mitochondrial biogenesis in muscle, drugs designed to mimic these exercise effects may prevent or improve diabetes. We will firstly establish if specific drug treatments that alter NO levels in muscle cells grown in culture alter mitochondrial biogenesis. These results will help us to clarify the role of NO in mitochondrial biogenesis. However, it is difficult to directly examine the effects of exercise in cultured cells. Therefore, further studies will then use real life models such as rodents that have been exercised to examine the role of NO and exercise on mitochondrial biogenesis. We will feed a drug to decrease NO levels in normal rats; and use mice, genetically altered to be lacking in NO to determine if these treatments decrease mitochondrial biogenesis that is normally seen following endurance exercise. Furthermore, since defects in mitochondrial biogenesis have such an important impact on diabetic humans, we will use humans to examine if differences in NO levels in skeletal muscle among type 2 diabetics or endurance-trained athletes correlate with mitochondrial biogenesis. Finally, we will infuse a drug into type 2 diabetics that increases NO in muscle to determine if it also increases mitochondrial biogenesis.Read moreRead less