Role Of Sphingolipid Signalling In Hepatic Insulin Resistance And Its Application In Prediction Of Risk For Type 2 Diabetes And Prediabetes
Funder
National Health and Medical Research Council
Funding Amount
$563,305.00
Summary
Type 2 diabetes is expected to reach epidemic proportions in the coming decades. Prediabetes is usually unrecognized and constitutes a major public health concern that needs earlier interventions, because the majority of prediabetic subjects proceed to T2D. We have identified an enzyme that plays an important role in insulin signalling. The possibility is that the level or activity of this enzyme is a potential biomarker of the prediabetes state and could be also used as a target
Conologues: Ultra-fast-acting Therapeutic Insulins Based On Cone Snail Venom Insulin Principles
Funder
National Health and Medical Research Council
Funding Amount
$1,082,866.00
Summary
The increasing prevalence of Type 1 and Type 2 diabetes demands better treatments. Our Project is based on a fascinating discovery by our international team of CIs of a new type of insulin within marine organisms that could form the basis of a novel diabetes therapeutic. Within our Project we will exploit this discovery to develop a new class of ultra-rapid-acting therapeutic insulins.
Metabolic Wiring In Adipocytes - Unique Role In Maintaining Long-term Health
Funder
National Health and Medical Research Council
Funding Amount
$1,077,886.00
Summary
Fat cell metabolism is wired to optimize the cell’s ability to make and store lipid while programming the cell to fulfil its function in whole body metabolism. We will: 1) map fat cell metabolism under optimal and insulin resistant conditions; 2) explore the role of 3 nodes in his metabolic circuit predicted as control points; 3) use a novel genetically engineered mouse model to explore the functional significance of fat cell metabolism in whole body insulin sensitivity.
The prevalence of type 2 diabetes in increasing worldwide, the International Diabetes Federation predicting 435 million will have diabetes in 2030. The major driver of the diabetes epidemic is obesity. There is strong evidence linking type 2 diabetes and obesity to an increased risk of cancer. However, the exact mechanism promoting cancer development in obese and diabetic individuals is not clear. This project will examine the effects of high insulin levels on cancer development and progression.
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.
Most common diseases of ageing like diabetes and cancer have proven intractable because much of our knowledge is limited to individual molecules. This proposal takes a global approach to complex diseases, utilising quantitative high-resolution methods and computational modelling. This research will lead to a completely new way of thinking about complex diseases providing a range of completely novel treatment options.
Neuronal Regulation Of Systemic Mitochondrial Stress
Funder
National Health and Medical Research Council
Funding Amount
$865,605.00
Summary
Mitochondria are the powerhouses of cells. They generate energy from the food we eat and air we breathe. However, excess nutrients can cause mitochondrial stress and damage that lead to disease. The objective of this research is to understand how the brain regulates mitochondrial stress responses throughout the body. Therefore, this project will identify stress-response processes that are directly relevant to health and disease.
Obesity is an important cause of disease, including liver disease. Obesity-associated liver disease occurs when the liver becoming resistance to the effects of insulin, the hormone that controls blood sugar (glucose). In muscle and fat, insulin causes glucose to be taken into the tissues and stored. Glucose is made in the liver and the actions of insulin here are to turn off the release of glucose into the circulation and increase uptake and storage of glucose. Insulin resistance occurs in a num ....Obesity is an important cause of disease, including liver disease. Obesity-associated liver disease occurs when the liver becoming resistance to the effects of insulin, the hormone that controls blood sugar (glucose). In muscle and fat, insulin causes glucose to be taken into the tissues and stored. Glucose is made in the liver and the actions of insulin here are to turn off the release of glucose into the circulation and increase uptake and storage of glucose. Insulin resistance occurs in a number of situations but the most important of these is obesity, particularly when there is accumulation of fat inside the abdominal cavity. Although the liver has a central role in co-ordinating the bodies response to insulin, the mechanisms of insulin resistance in human liver are unknown. One prominent hypothesis is that fat molecules released by intra-abdominal fat deposits are responsible. Intra-abdominal fat stores are important because fatty acids from these deposits can travel directly to the liver with the blood supply from the gut. However the precise effects of these on insulin action in the liver are unknown. Fat tissue is actively involved in the regulation of metabolism and releases a number of regulatory proteins. One of these, adiponectin, appears to have an important role in improving insulin sensitivity in the liver. The production of adiponectin decreases as obesity increases, providing another link between obesity and insulin resistance in the liver. This project will examine insulin action and the signalling molecules responsible for this in human liver tissue. The project aims to determine the effect of obesity, particularly intra-abdominal fat deposits, on insulin responses in liver tissue. The studies also aim to confirm (or otherwise) the role of free fatty acids and adiponectin on insulin action in human liver. The data from these studies will contribute to our understanding of insulin resistance and obesity-related liver disease.Read moreRead less
Dissecting The Role Of Selective Insulin Resistance In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$980,624.00
Summary
Insulin resistance is a clinical condition where insulin, secreted from the pancreas in response to meals, is unable to fulfill its normal function. It is intimately linked to obesity and associated diseases - type 2 diabetes, cancer and cardiovascular disease. This proposal examines mechanisms contributing to insulin resistance and how insulin resistance leads to disease. We will identify drug targets with improved specificity and lead to novel insight into the risks of current treatments.