Childhood diabetes [both type 1- and young type 2-] is increasing alarmingly. Diabetes prevention will be a great benefit via both a healthier population and relief to the national health budget. To develop targeted preventive treatments we first need to identify genetic risk factors, requiring access to a large number of samples. We will establish a national Repository which will make DNA available to all qualified Australian researchers enhancing their ability to identify causes of diabetes.
A Longitudinal Study Of Nerve Morphology In Diabetic Neuropathy Using Novel Non-invasive Ophthalmic Surrogate Markers
Funder
National Health and Medical Research Council
Funding Amount
$540,372.00
Summary
This research project will use two new ophthalmic instruments - the corneal confocal microscope and non-contact corneal aesthesiometer - to directly monitor changes in corneal nerves and corneal sensitivity, over a 5 year period, in diabetic patients suffering from a painful condition of the arms and legs known as diabetic neuropathy. This study will generate important new information that could allow diabetic doctors to more accurately monitor the progression of the disease.
Short-term Effects Of Overfeeding On Metabolic Risk In Humans
Funder
National Health and Medical Research Council
Funding Amount
$417,196.00
Summary
The prevalence of obesity is rapidly increasing in Australia and other parts of the world. Obesity is closely associated with insulin resistance and plays a role in the development of type 2 diabetes. However, the effects of short-term periods of over nutrition in humans remain unclear. In the proposed study, we will investigate the effects of short-term weight gain by high fat feeding in lean subjects, in subjects who are overweight and in subjects who are genetically more likely to develop dia ....The prevalence of obesity is rapidly increasing in Australia and other parts of the world. Obesity is closely associated with insulin resistance and plays a role in the development of type 2 diabetes. However, the effects of short-term periods of over nutrition in humans remain unclear. In the proposed study, we will investigate the effects of short-term weight gain by high fat feeding in lean subjects, in subjects who are overweight and in subjects who are genetically more likely to develop diabetes (due to strong family history). The aims are to distinguish physiological and endocrine characteristics of individuals who store more fat in response to overfeeding. We will identify differences between these individuals and whether they have defects in upregulating machinery involved in fat oxidation and energy production in skeletal muscle that may help them adapt during to energy excess. We will look for changes in type 2 diabetes risk and we will have the potential to identify defects in factors that are involved in this response. We will also re-examine indivudals again after calorie restriction and weight loss. We also plan to confirm the role of the candidate genes involved in fat oxidation that have been identifieid in human studies by in vivo gene transfer technology in rodents. This study will determine whether overweight and lean subjects behave similarly when faced with an overfeeding challenge. We expect that individuals with a genetic predisposition for T2DM will become more IR, due to metabolic inflexibility and a decreased ability to upregulate machinery involved in fatty acid oxidation and mitochondrial function. By characterising the physiological and endocrine responses to overfeeding, we will establish quantifiable markers allowing us to distinguish those at risk and identify new targets for pharmacological or lifestyle intervention.Read moreRead less
The Role Of Hypoxia Inducible Factor 1a In Beta-Cell Function And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$362,303.00
Summary
HIF1a is a gene which our preliminary data shows is needed for normal beta-cell function and insulin secretion. When beta-cells cannot release enough insulin, blood sugar levels rise, and diabetes develops. This research plan will look at the effects of deletion of HIF1a and of increasing HIF1a to see how this affects function of beta-cells and - or diabetes development. This work may show that HIF1a is a potential therapeutic target for the treatment of diabetes in humans.
Does Loss Of Melanocortin Glucose Sensing Contribute To Obesity Induced Diabetes?
Funder
National Health and Medical Research Council
Funding Amount
$617,531.00
Summary
Diabetes is a failure to properly regulate blood glucose levels. Escalating rates of diabetes are a major health problem. Melanocortin neurons in the brain detect blood sugar levels and usually regulate glucose production and utilization, but in obese animals they do not. We have developed a possible therapeutic, which appears to reverse the glucose insensitivity, and rapidly reduces blood glucose in diabetic mice. This project will determine how melanocortins act to regulate glucose levels
Short Term Effects Of Overfeeding On Metabolic Risk In Humans
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Obesity is associated with increased risk of diabetes, heart disease and cancer. Obesity prevalence is rapidly increasing and consitutes one of the greatest threats to human health. The aim of this study is to determine mechanism-s underlying the close relationship between obesity and insulin resistance by inducing experimental weight gain in humans with and without a genetic predisposition to diabetes. This project will help identify new candidates for anti-diabetes drugs.
Gene Variants In Adiponectin And Its Receptors As Risk Factors For Metabolic And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$534,107.00
Summary
Obesity has a major impact on the development of metabolic syndrome (MetS), type 2 diabetes (T2D), and cardiovascular disease (CVD). It is important to identify the molecular links between obesity and these conditions. Adiponectin, an adipocyte-specific hormone, is a likely molecular candidate because of its pleiotropic metabolic actions. We will investigate the role of adiponectin, the variants within its gene ADIPOQ, and that of its two receptors, in the development of MetS, T2D, and CVD.
A Single Fibre Study Of The Relationship Between Glucose Transport And Skeletal Muscle Contractility
Funder
National Health and Medical Research Council
Funding Amount
$284,625.00
Summary
Type 2 diabetes (a progressive disorder often accompanied by obesity) is claimed to be the most common metabolic disease in the world and is predicted to affect 1.15 million Australians by the year 2010. Muscle contraction (in the form of physical exercise or exercise training) is now an essential component in the management of type 2 diabetes and-or obesity.This project has been planned from a perspective that combines theoretical and experimental expertise in the field of muscle cell contracti ....Type 2 diabetes (a progressive disorder often accompanied by obesity) is claimed to be the most common metabolic disease in the world and is predicted to affect 1.15 million Australians by the year 2010. Muscle contraction (in the form of physical exercise or exercise training) is now an essential component in the management of type 2 diabetes and-or obesity.This project has been planned from a perspective that combines theoretical and experimental expertise in the field of muscle cell contractility with a keen interest in the role of skeletal muscle in glucose homeostasis. Work carried out within the scope of this project will contribute new insights into the pathogenesis of type 2 diabetes-obesity and new information on the cellular mechanisms involved in contraction-stimulated glucose transport by skeletal muscle. As part of this project we will develop single muscle cell-fibre preparations and appropriate protocols for monitoring cellular aspects of glucose transport in skeletal muscle. These preparations-protocols will have the potential to be used for testing anti-diabetic drugs directed towards intracellular targets. From an educational benefit point of view, the project will create the opportunity for 4-6 honours and 2-3 PhD students to acquire a rare and useful combination of skills and expertise in muscle cell biochemistry and physiology, while working on an issue of medical concern.Read moreRead less
Muscle Derived Interleukin-6: Signalling Pathways And Biological Roles
Funder
National Health and Medical Research Council
Funding Amount
$330,375.00
Summary
Over the past few years work from our research group has identified that the cytokine interleukin-6 (IL-6) is produced by skeletal muscle during contractions. Moreover, we have demonstrated that IL-6 performs entirely novel functions that have major ramifications for diseases such as type 2 diabetes and obesity. We have demonstrated that IL-6 is a potent factor in increasing the breakdown of fatty acids in the human body. We have also demonstrated that IL-6 down-regulates the cytokine tumour nec ....Over the past few years work from our research group has identified that the cytokine interleukin-6 (IL-6) is produced by skeletal muscle during contractions. Moreover, we have demonstrated that IL-6 performs entirely novel functions that have major ramifications for diseases such as type 2 diabetes and obesity. We have demonstrated that IL-6 is a potent factor in increasing the breakdown of fatty acids in the human body. We have also demonstrated that IL-6 down-regulates the cytokine tumour necrosis factor alpha (TNF-a), which impairs glucose uptake and promotes insulin resistance. The proposed work will extend upon these findings. Discovering that IL-6 produced during exercise contributes to fatty acid utilisation will have profound ramifications for what we know about energy breakdown. If we find that the function of IL-6 produced by muscle is to down-regulate TNF-a and lead to enhanced glucose uptake in type 2 diabetics, it may lead to IL-6 being used as a possible therapeutic aid in the treatment of type 2 diabetes. In summary, this project will have major significance for not only our fundamental knowledge of the processes involved in maintaining metabolic homeostasis, but also for our understanding of the major health problem of obesity related diseases.Read moreRead less