Alterations In Secretion And Gene Expression In Pancreatic Beta Cells Exposed To Lipid.
Funder
National Health and Medical Research Council
Funding Amount
$425,250.00
Summary
The project is aimed at a better understanding of the way in which fats control gene expression in the pancreatic beta cells of the islets of Langerhans. Because changes in gene expression are to likely to explain why exposure of these cells to fat disrupts their ability to release insulin, identification of these genes could explain why only some obese people develop Type 2 diabetes.
Mitochondrial Energy Metabolism And Insulin Action
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Obesity and type 2 diabetes are two major health conditions associated with abnormal energy metabolism. In this proposal I will investigate the role of important metabolic proteins in regulating energy expenditure and insulin action in skeletal muscle and adipose tissue, two crucial tissues for whole-body energy metabolism. These studies will provide critical insight into the factors leading to obesity and type 2 diabetes and will assist in identifying possible therapeutic targets.
Correlative Structure-function Studies Of Cis- And Trans-Golgi Membrane Traffic In Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$649,531.00
Summary
This project combines imaging by light and electron microscopy with additional techniques for studying protein function at the molecular level, to elucidate how changes in the 3D organisation of cellular machinery can lead to fundamental changes in the function and health of mammalian cells. Although this work includes detailed investigation of the 'insulin factory', it has the potential to modify established concepts on membrane traffic and protein secretion well beyond the field of diabetes.
ACTIVATION OF ISLET INFLAMMATION BY CYTOKINE SIGNALING IN PANCREATIC BETA CELLS
Funder
National Health and Medical Research Council
Funding Amount
$406,838.00
Summary
Type 1 diabetes affects up to 4.7 million people world-wide and its incidence is increasing. It is the result of killing of insulin-producing pancreatic beta cells by cells of the immune system. This project aims to understand how immune cell invasion of the pancreas can become worse because of protein interactions that occur within beta cells, and how these cells can contribute to their own demise.
Ciliary Neurotrophic Factor: A Novel Theraputic Agent For The Prevention Of Muscle Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$602,673.00
Summary
In 1995 leptin was discovered and scientists world-wide hoped that this was the great panacea in the treatment of obesity related disorders. Alas, from 1995-1997 the identification of a novel cytokine inducible compound termed suppressor of cytokine signaling (SOCS) that negatively regulated leptin signalling and lead to leptin resistance, quashing hopes for a viable anti-obesogenic drug. Recently, however, work from our group has demonstrated that the neuropoietic cytokine, ciliary neurotrophic ....In 1995 leptin was discovered and scientists world-wide hoped that this was the great panacea in the treatment of obesity related disorders. Alas, from 1995-1997 the identification of a novel cytokine inducible compound termed suppressor of cytokine signaling (SOCS) that negatively regulated leptin signalling and lead to leptin resistance, quashing hopes for a viable anti-obesogenic drug. Recently, however, work from our group has demonstrated that the neuropoietic cytokine, ciliary neurotrophic factor (CNTF), can act in an anti-obesogenic fashion in a manner similar to leptin. However, unlike leptin, when we place rodents on a high fat diet, the effects of CNTF persist and override induction SOCS proteins. This project will examine the biochemical pathways that allow the actions of CNTF to persist in the presence of diet-induced obesity. This is of major significance because in completing this work, the potential for the development of peripheral tissue drug targets for the treatment of obesity related diseases are both tangible and realistic.Read moreRead less
Elucidating The Molecular Regulation Of Gp130 Complex Signalling In Lipid And Glucose Metabolism.
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Overnutrition promotes obesity, which greatly increases the risk of type 2 diabetes and cardiovascular disease. We have provided evidence that activation of gp130 signalling may enhance insulin action and fatty acid oxidation in metabolically active tissues. My research proposal aims to elucidate the molecular regulation of gp130 complex signalling in lipid and glucose metabolism in important metabolic tissues.
I am a biochemist determining how metabolism is controlled in response to energy supply and demand. This is important in order to understanding how diet and exercise are beneficial to health.
A Novel Lipid Sensitive Kinase And Its Role In Obesity-induced Inflammation And Insulin Resistance.
Funder
National Health and Medical Research Council
Funding Amount
$560,045.00
Summary
It is now apparent that obesity leads to chronic low grade inflammation which results in insulin resistance or pre-diabetes. The mechanisms that link obesity-induced inflammation to insulin resistance are not well understood, but involve lipid oversupply. We have preliminary data identifying that a protein, not known to previously play a role in metabolic diseases, is a critical mediator of lipid-induced inflammation. We will investigate the clinical potential of blocking this protein.
Can Blocking Fatty Acid Transport In Myeloid Cells Prevent Insulin Resistance?
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Over the past 5 years it has become apparent that blood cells can become inflamed as people become obese. These inflamed blood cells can contribute to insulin resistance or pre-diabetes. Our hypothesis is that these blood cells become inflamed because they take up fat via fatty acid transporters. Our approach is to knock out one of these fatty acid transporters specifically in blood cells and reduce inflammation and insulin resistance due to overnutrition.