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
A lipodomic approach to cnidarian-dinoflagellate symbiosis. Fatty Acids are essential for human health and for reef health. This lipodomic study using newly developed techniques, aims to understand the essential and non-essential fatty acid metabolic exchange in the symbiosis that drives coral reef formation and health, and in turn gives reflective insight into our own metabolism.
Molecular control of embryonic diapause. Many species can halt growth of the early embryo (diapause). This project will use novel animal models and new proteomics techniques to clarify what signals from the uterus control diapause of the embryo. This may uncover new mechanisms for cell regulation that will be relevant to the biology of stem cells, cancer and reproductive technologies.
Role of suppressor of cytokine signalling proteins (SOCS3) in defective muscle repair and ageing. Old muscles are slower and weaker than young muscles, they are injured more easily and they repair less successfully. This proposal investigates the role of SOCS3-signalling in muscle repair, ultimately to improve healing and to promote healthy ageing that will enable older Australians to enjoy a better quality of life.
Matching Supply And Demand: How Does Metabolism Fine-tune Signal Transduction?
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
Insulin controls nutrient traffic and disrupting its actions are linked to many diseases: type 2 diabetes, cancer, heart disease. Here, I will test a novel hypothesis that our cells’ metabolic rate, defined by the balance between nutrient supply and energy expenditure, controls how cells respond to insulin. These metabolic regulatory nodes would play a major determinant of many essential functions linked to human health, and thus provide novel therapeutic targets for numerous diseases.
Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.
Identifying The Critical Components Of Growth Factor-mediated Survival Pathways
Funder
National Health and Medical Research Council
Funding Amount
$589,338.00
Summary
The regulation of cell lifespan (cell survival) is controlled by growth factors and lies at the heart of all biological processes. However, little is known of the molecular switches inside cells that either turn survival on or off. We propose to identify and characterize the molecular switches inside cells that control the balance between cell survival and death. Targeting specific components of these switches may provide new approaches for the treatment of cancer and infectious diseases.
Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems ar ....Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems are activated as during the process.Read moreRead less
Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. ....Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. Understanding fat breakdown is also important for developing new processing technologies in the food industry.Read moreRead less
Molecular basis of skeletal muscle lipoapoptosis. High levels of fat in cells are associated with obesity and type 2 diabetes, medical conditions that have increased dramatically in prevalence in Australia. High fat levels in cells also causes cell death. This research will determine the mechanisms by which excessive fat storage leads to cell death and whether this leads to insulin resistance and type 2 diabetes. By understanding this relationship, effective pharmaceutical treatments will be dev ....Molecular basis of skeletal muscle lipoapoptosis. High levels of fat in cells are associated with obesity and type 2 diabetes, medical conditions that have increased dramatically in prevalence in Australia. High fat levels in cells also causes cell death. This research will determine the mechanisms by which excessive fat storage leads to cell death and whether this leads to insulin resistance and type 2 diabetes. By understanding this relationship, effective pharmaceutical treatments will be developed that will ultimately reduce the incidence of type 2 diabetes, and ease the associated financial burden on the community and healthcare system.Read moreRead less