Targeting Skeletal MTORC1 As A Novel Approach For The Treatment Of Diet-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$586,979.00
Summary
Diet-induced insulin resistance is a pathology that underlies type 2 diabetes. Elucidating the pathways and tissues that contribute to this condition is crucial for drug development. The skeleton has emerged as a critical insulin target tissue. We provide evidence that suppression of mTORC1, a complex over-activated by nutrients, in bone cells improves insulin sensitivity. In this study, we will determine if blocking mTORC1 function in bone cells can treat diet-induced insulin resistance.
Function And Pathophysiological Role Of A Novel Glucose Transporter Expressed In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$216,412.00
Summary
Diabetes is a disorder of metabolism resulting from a combination of deficiency of insulin and defective action of the insulin that is present. The most prominent metabolic abnormality is high blood glucose, which is often not satisfactorily corrected by insulin treatment. One of the main reasons for the high blood glucose is reduced uptake of glucose by muscle tissue. The mechanism by which insulin enhances glucose entry into muscle cells involves mobilisation of a specific protein from the glu ....Diabetes is a disorder of metabolism resulting from a combination of deficiency of insulin and defective action of the insulin that is present. The most prominent metabolic abnormality is high blood glucose, which is often not satisfactorily corrected by insulin treatment. One of the main reasons for the high blood glucose is reduced uptake of glucose by muscle tissue. The mechanism by which insulin enhances glucose entry into muscle cells involves mobilisation of a specific protein from the glucose transporter protein family, which has been designated GLUT4. Surprisingly, animals that have been genetically altered to eliminate orknockout GLUT4 production do not develop diabetes. This finding has led to the theory that there is a backup glucose transporter protein that can prevent diabetes when there is a problem with GLUT4 function. We have recently discovered a new member of the glucose transporter protein family that could potentially function as either a parallel or a backup system for GLUT4. This new glucose transporter, which we have called GLUT8, is present in human muscle tissue and studies in other cells have shown that it alters its distribution within the cell in reponse to insulin. We now want to study in more detail the role of this new glucose transporter in muscle tissue and how it functions compared with GLUT4. In particular, we think it is possible that Type 2 diabetes occurs when there is not only a problem with the mobilisation of GLUT4 but also a defect in the production or function of GLUT8. If this is the case, then increasing GLUT8 production might improve glucose transport into muscle tissue and so improve control of blood glucose levels in diabetes.Read moreRead less
Regulation Of Glucose Uptake By Tropomyosins And Myosins
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
Defective import of glucose from the blood into fat and muscle is a key cause of adult-onset diabetes. We have identified a novel mechanical structure within muscle and fat cells defined by the protein tropomyosin that is involved in glucose import and potentially provides new targets for treatment of adult-onset diabetes and obesity.
Glutathione Transferase Zeta: A Novel Regulator Of Glucose And Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$604,143.00
Summary
Obesity is a problem of global significance as a cause of preventable illness and death. The many consequences of obesity including cardiovascular disease, type 2 diabetes, cancer and osteoarthritis are an increasing burden on affected subjects and on the health care system. Our recent studies have revealed a novel pathway for the regulation of obesity. This discovery has provided a new target for the development of drugs for obesity and related disorders.
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.
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.
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.
Manipulation Of Energy Metabolism To Control Lipid Accumulation And Insulin Action.
Funder
National Health and Medical Research Council
Funding Amount
$804,106.00
Summary
I am a metabolic biochemist investigating how overconsumption of calories, particularly fat, results in dysfunctional energy metabolism and increased the risk of type 2 diabetes. I examine changes in the daily rhythms of energy intake, energy utilisation and energy storage in different tissues of dietary and genetically modified animals to pinpoint novel ways of reducing fat accumulation and reducing the risk of type 2 diabetes.
Transcription-based Identification Of Insulin Resistance Subtypes
Funder
National Health and Medical Research Council
Funding Amount
$341,883.00
Summary
A key feature of type 2 diabetes is the failure of metabolic tissues such as muscle and fat to respond to normal levels of insulin. This 'insulin resistance' is caused by a number of mechanisms. We will use cutting-edge technology to identify small sets of genes that define each variety of insulin resistance. These gene sets will be used to diagnose sub-types of insulin resistance and will facilitate the development of personalised therapies to effectively treat individuals with type 2 diabetes.