Inhibition Of AMPK Signalling As A Strategy For Decreasing Appetite
Funder
National Health and Medical Research Council
Funding Amount
$644,266.00
Summary
The enzyme AMP-activated protein kinase (AMPK) has previously been implicated in mediating increased food intake in response to fasting and the appetite-inducing hormone ghrelin. In this study we propose to investigate whether inhibition of AMPK has promise as a strategy to reduce hunger in the context of dietary restriction and increases in energy expenditure, such as exercise. We will also test whether a new AMPK inhibitor has the potential to reduce appetite signalling in cells and in mice.
The key goal of my research is to understand the role of protein phosphorylation in controlling metabolism, with a special emphasis on the structure and function of members of the AMP-activated protein kinase (AMPK) pathway. This is important because the function and survival of all organisms is dependent on the dynamic control of energy metabolism, with energy demand matched to energy supply.
Targeted Development Of AMPK Β2-isoform Allosteric Activators
Funder
National Health and Medical Research Council
Funding Amount
$898,147.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to dramatic increases in the incidence of diseases associated with metabolic dysregulation e.g. type 2 diabetes. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as a cellular fuel gauge. We have discovered a new drug that crucially activates the form of AMPK found in metabolically active organs. We aim to develop this drug to unlock new therapeutic opportunity.
Control Of Anabolic And Catabolic Pathways By AMPK
Funder
National Health and Medical Research Council
Funding Amount
$946,402.00
Summary
This project focuses on the role of the metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) in the control of glucose and fat metabolism. AMPK has been linked to the regulation of exercise capacity, longevity and the control of insulin sensitivity. This is important for our understanding of the metabolic dimensions of our Nations most important health problems including, type-2 diabetes, cardiovascular disease, obesity, neurodegeneration as well as other age onset diseases.
Metabolic Stress Sensing By AMPK: Implications For Energy Balance And Isoform-targetting Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$632,188.00
Summary
Metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease impose enormous medical and economic burdens on Western societies. Our research is focussed on the enzyme AMP-activated protein kinase (AMPK) which acts as the fuel gauge of the cell and is a promising drug target for combating metabolic diseases. Our discoveries provide critical insight on how AMPK is switched on by both energy demand and drugs, and will greatly assist development of AMPK-targetted therapeutics.
The Role Of Protein Kinase C Epsilon In The Generation Of Lipid-Induced Insulin Resistance In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$474,750.00
Summary
Insulin normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized by a failure of these tissues to respond adequately to insulin. This loss of sensitivity to the hormone is known as insulin resistance, and has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. Certain fat molecules are able to cause the activation of pathways within cells which can in ....Insulin normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized by a failure of these tissues to respond adequately to insulin. This loss of sensitivity to the hormone is known as insulin resistance, and has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. Certain fat molecules are able to cause the activation of pathways within cells which can interfere with the normal signalling of insulin. We have recently found that mice lacking an enzyme thought to be involved in such negative pathways are less susceptible to insulin resistance caused by high-fat feeding. The aim of this project is to investigate the mechanism by which this enzyme contributes to inhibition of insulin action. We will determine the step in normal insulin signalling which is blocked by the activation of the enzyme upon increased fat supply. This will help us to determine the pathway leading from the enzyme to insulin signalling. We will also identify the particular form of fat which leads to activation of the enzyme. This work will lead to a better understanding of the mechanisms by which fats can play a role in the generation of insulin resistance, so that they can be targeted both for the development of new and more effective treatments for the disorder and for prevention of its onset.Read moreRead less
AMPK Control Of Lipid Metabolism: Role In Regulating Energy Balance And Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$614,437.00
Summary
The control of appetite and maintenance of a lean body mass along with exercise is important for protecting the body against obesity and increased incidence of Type 2 diabetes and cardiovascular disease. We are investigating how the regulation of lipid metabolism controls appetite and body weight and the extent to which these same controls are important for drugs acting to lower blood lipid levels.