Modulating Gastrointestinal Function For Control Of Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$883,469.00
Summary
It is now recognized that gastrointestinal function, particularly the rate that meals empty from the stomach, and the secretion of hormones from the small intestine in response to nutrients, is fundamental to blood glucose control in people with diabetes. This project seeks to understand how these processes can best be modified by dietary or pharmaceutical means to improve blood glucose control and thereby prevent complications in type 2 diabetes
Fat Sensing In The Gut: Role In Appetite Regulation In Health And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$391,076.00
Summary
Dr Little has an international reputation for her research relating to the sensing of nutrients in the gut. During the next 4 years her goal is to establish herself as an independent researcher leading a team and program focussed on characterising the molecular and physiological mechanisms by which fat is sensed in the gut, and the role of these mechanisms in energy intake regulation in health and obesity. These insights are likely to result in more effective management strategies for obesity.
Mechanisms Regulating Nutrient Induced Motor Patterns In The Isolated Small Intestine
Funder
National Health and Medical Research Council
Funding Amount
$427,750.00
Summary
The movements of the small intestine are essential for the digestion and absorption of a meal and consist of two basic patterns during a 3-4 hour period after a meal. These are mixing (or segmentation) and propulsion (or peristalsis). Although it is the subject of ongoing study, much is known about the basic mechanisms that control propulsion, largely because this behaviour is readily seen in isolated segments of gut so it is possible to undertake highly controlled experiments to identify the va ....The movements of the small intestine are essential for the digestion and absorption of a meal and consist of two basic patterns during a 3-4 hour period after a meal. These are mixing (or segmentation) and propulsion (or peristalsis). Although it is the subject of ongoing study, much is known about the basic mechanisms that control propulsion, largely because this behaviour is readily seen in isolated segments of gut so it is possible to undertake highly controlled experiments to identify the various cellular components of the system. By contrast, mixing has only been reliably seen in intact animals making studies of the detailed mechanisms responsible for this behaviour much more difficult. What is known is that the composition of a meal controls the relative amount of mixing and propulsion seen at any location along the small intestine. We have recently identified a pattern of contractions in isolated small intestine (duodenum and-or jejunum) that is induced by the presence of a nutrient in the intestine and appears very similar to the mixing behaviour seen in the intact animal. We have shown that this pattern depends on the activity of nerve cells including those that excite the gut muscle and that it depends on the activity of a hormone released from the lining of the gut wall by fats and other nutrients. The aims of this proposal are to identify how nutrients interact to produce this pattern of contractions, the relative roles of specific types of nerve cells and the sites at which the local hormones released by nutrients act. This is important because increasing the proportion of mixing to propulsion enhances the absorption of nutrient from a meal, so if the mechanisms that initiate mixing behaviour can be regulated in a predictable way by specific nutrient, absorption can be enhanced in various malabsorption syndromes.Read moreRead less
Transcutaneous Electrical Stimulation To Relieve Chronic Constipation In Children
Funder
National Health and Medical Research Council
Funding Amount
$82,450.00
Summary
1 in 300 children suffer from chronic constipation that is not fixed by changing their diet or taking laxatives. They continue to suffer the problem into adulthood. They also have fecal incontinence or soiling that causes problems with socialising and schooling. We are testing a method of electrical stimulation through the skin on the belly to increase the movement of the bowel. Initial results are encouraging, showing that the rate of movement of the bowel is increased and soiling is decreased.
Transcutaneous Electrical Stimulation To Relieve Chronic Constipation In Children
Funder
National Health and Medical Research Council
Funding Amount
$346,995.00
Summary
We have over 300 children with chronic treatment-resistant constipation at Royal Children's Hospital Melbourne. We have a new physiotherapy technique that may overcome constipation and stop soiling in many of these children. In 2003-4, we ran a pilot study to test a technique used by physiotherapists to treat urinary incontinence. We have called the method TESIC (transcutaneous electrical stimulation using interferential current). TESIC uses suction electrodes placed on the belly and back at the ....We have over 300 children with chronic treatment-resistant constipation at Royal Children's Hospital Melbourne. We have a new physiotherapy technique that may overcome constipation and stop soiling in many of these children. In 2003-4, we ran a pilot study to test a technique used by physiotherapists to treat urinary incontinence. We have called the method TESIC (transcutaneous electrical stimulation using interferential current). TESIC uses suction electrodes placed on the belly and back at the level of the belly button. The electrical stimulation is applied using a current (interferential current) that stimulates deep into the abdomen. We tested 8 children and had very encouraging results with improved constipatio in 5-8 and all with soiling stopped. Parents and children are keen to use this technique but first we need to establish that the results are reproducible in a larger group of 70 children. We also need to know if the effect was just a placebo response (due to time spent with the physiotherapists), and how long the effect lasts. We will also measure changes in soiling. Faecal soiling is smelly and antisocial. Relief of soiling has a big impact on a child's ability to fit in at school and to attend normal schooling. We will measure outcomes using daily diaries kept by children, questionnaires, how quickly food moves through the bowel and pressures within the bowel. We have a multidiciplinary team of experienced clinicians and scientists with expertise in these techniques and in constipation and incontinence in children (paediatric surgeon, gastroenterologist, manometry nurse, incontinence paediatrician and physiotherapist, expert in electrical stimulation and gut nervous system scientist). This technique could revolutionise treatment of chronic constipation. Most physiotherapists have TESIC machines, allowing delivery Australia wide. It is non-invasive and should also be able to be used by adults, including the elderly in nursing homes.Read moreRead less
How Spinal Afferent Nerves Cause Vasodilation Of Mesenteric Arteries
Funder
National Health and Medical Research Council
Funding Amount
$353,250.00
Summary
Healthy function of the gastrointestinal tract requires an adequate blood supply during periods of varying demand. Inadequate blood supply to the gut contributes to disorders ranging in severity from mild through to lethal. Reduced blood supply to the gut is a trigger for multiple organ failure syndrome; a leading cause of death in critically ill patients following major surgery, trauma or haemorrhage. It is believed that damage to the lining of the gut, during periods of reduced flow, trigger i ....Healthy function of the gastrointestinal tract requires an adequate blood supply during periods of varying demand. Inadequate blood supply to the gut contributes to disorders ranging in severity from mild through to lethal. Reduced blood supply to the gut is a trigger for multiple organ failure syndrome; a leading cause of death in critically ill patients following major surgery, trauma or haemorrhage. It is believed that damage to the lining of the gut, during periods of reduced flow, trigger inflammatory mechanisms throughout the body. Mesenteric ischaemia is a disorder which occurs as a chronic, non-occlusive form, or as acute episodes, which are often lethal, . Temporary increases in blood supply are also known to play a vital role in protecting the gut from acid, toxins and attack by pathogens. The major mechanism underlying increases in bloody supply is dilation of arterial vessels. This occurs focally, at the site of damage, via local mechanisms, but this is supplemented by a more widespread dilation of arteries upstream, mediated by branches of sensory neurones that innervate blood vessels directly. Currently, there is no information about how these sensory neurones are activated. This is crucial to understand how they work. We hypothesise that these sensory neurones are activated by chemical and mechanical stimuli in the gut wall, which make them release vasodilator chemicals onto the arteries upstream and thus amplify the local increases in blood flow. We will test this by recording from sensory nerves, identifying the ones which project to blood vessels and determine which chemicals and mechanical stimuli they are excited by. We will then fill them with dye, using a method that we have recently developed, to visualise their branching patterns both inside and outside the gut wall. In this way, we will understand how this powerful protective mechanism is activated at times of need, and how it may fail under some circumstances.Read moreRead less
Sensory Innervation Of The Anal Region In Normal And Diabetic Guinea Pigs
Funder
National Health and Medical Research Council
Funding Amount
$372,389.00
Summary
Until something goes wrong, we take it for granted that we can empty our bowels on a regular basis, at a time and place of our choosing. Failure to achieve this is very distressing and substantially diminishes quality of life, if it occurs regularly. Disordered defecation, fecal incontinence and constipation are surprisingly common and their prevalence will continue to increase as our population ages and the incidence of diseases such as diabetes increases. In many people suffering these problem ....Until something goes wrong, we take it for granted that we can empty our bowels on a regular basis, at a time and place of our choosing. Failure to achieve this is very distressing and substantially diminishes quality of life, if it occurs regularly. Disordered defecation, fecal incontinence and constipation are surprisingly common and their prevalence will continue to increase as our population ages and the incidence of diseases such as diabetes increases. In many people suffering these problems, there is a detectable dysfunction of the sensory nerves in the anal region. These nerves supply information from the anal region to the spinal cord that can cause us to sense activity in our lower bowel and initiate defecation reflexes. These sensory pathways are important for clinical gastroenterology, but remarkably little is known about them. We are now able to investigate what it is the sensory nerves in the anal region sense, what they look like and where they go to in the spinal cord - in a single project. To do this we will use simple, but novel techniques that have been developed in this laboratory in an animal model. Once we know this, we will compare the function of sensory nerves in the anal region in diabetic animals with normal animals. This will give us insight into the role of sensory nerves in the development of fecal incontinence an unpleasant symptom for many people suffering advanced diabetes. My systematic approach will provide understanding of the basic cellular mechanisms and nerve pathways that underlie sensation in the anal region, helping both clinicians and patients understand the cause of defecatory disorders and potentially pointing the way to new therapies and strategies for diagnosis.Read moreRead less
TRANSCUTANEOUS ELECTRICAL STIMULATION TO TREAT CONSTIPATION DUE TO ANORECTAL RETENTION IN CHILDREN
Funder
National Health and Medical Research Council
Funding Amount
$635,320.00
Summary
If you don't poop, you die! Over 20% of older people have constipation. It starts in childhood in 1/100 people and lasts through life. At the Royal Children’s Hospital, Melbourne, we have been developing a physiotherapy method using electrical stimulation across the skin to treat long-term constipation. In this study we are comparing this treatment to current treatment in the most common type of chronic constipation in children.