Glucose is a critical fuel for living organisms and its presence in the gut triggers nerves that slow stomach emptying. However, little is known of how glucose is actually detected in the gut. We have established that sweet taste molecules of the tongue are also present in the gut, where they may detect glucose. This research will measure the expression and function of these molecules in the gut of humans and mice, and reveal key information on their potential as targets in health and disease.
Activated Protein C Utilises Protease Activated Receptors And Epidermal Growth Factor Receptor To Heal Wounds
Funder
National Health and Medical Research Council
Funding Amount
$436,882.00
Summary
Chronic leg ulcers are a major burden to the individual sufferer and to the health system. We have discovered that activated protein C (APC) potently stimulates wound healing in the laboratory and now have exciting positive results from a small pilot clinical trial showing that applying APC solution to leg ulcers also helps healing in patients. This study plans to discover how APC works at the molecular level.
Mechanics Of Normal And Disordered Gastric Emptying Studied Using Simultaneous Ultrasound And High Resolution Manometry
Funder
National Health and Medical Research Council
Funding Amount
$145,626.00
Summary
Optimal digestion and absorption relies on the stomach breaking down food and delivering it to the small intestine at an optimal rate. Abnormalities in the processes controlling the stomach's processing of food may lead to malnutrition, gastrointestinal symptoms or unpredictable drug absorption, and are commonly seen in patients with diabetes mellitus, gastrointestinal reflux disease and nonulcer dyspepsia, or following stomach surgery. Currently our understanding of the way the stomach empties ....Optimal digestion and absorption relies on the stomach breaking down food and delivering it to the small intestine at an optimal rate. Abnormalities in the processes controlling the stomach's processing of food may lead to malnutrition, gastrointestinal symptoms or unpredictable drug absorption, and are commonly seen in patients with diabetes mellitus, gastrointestinal reflux disease and nonulcer dyspepsia, or following stomach surgery. Currently our understanding of the way the stomach empties food is incomplete, and there is little information as to the mechanisms by which diseases cause abnormal stomach emptying. Recent developments in recording methods mean that we can now simultaneously measure stomach contractions, the pressures these generate and flow from the stomach. This information is synchronised and displayed for analysis using computer techniques. In this project these novel methods will be used initially to examine the normal processes by which meals with a variety of compositions and consistencies empty from the stomach. This will provide information as to which aspects of the way the stomach functions are important for breaking down food into particles, and which aspects control the flow of food from the stomach into the intestine. The mechanisms by which the rate of emptying of the stomach is controlled by feedback signals caused by the presence of foodstuffs in the small intestine will be investigated by examining the effects of infusing nutrients into the intestine on the motions of the stomach wall, pressures within the stomach and the passage of stomach contents into the small intestine. The mechanism of action of drugs and diseases which slow stomach emptying will then be examined by measuring the movements, pressures and emptying of the stomach in subjects receiving the drug, or in patients with dibetes, and comparing this information with the processes observed during normal stomach emptying.Read moreRead less
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
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.
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.
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