Clinical Modulation Of The Hyperglycaemic Effect Of A 10-second Sprint In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$567,207.00
Summary
Although regular exercise provides a number of health benefits for individuals with Type 1 diabetes, it increases the risk of hypoglycaemia, which if severe can result in convulsion, coma and irreversible brain damages. Recently, we have made the surprising discovery that it is possible to prevent hypoglycaemia if exercise is combined with one or several short sprints. Our goal is to identify some of the clinical factors likely to interfere with the glucoregulatory benefits of sprinting.
Mechanisms Of Hypoglycaemic Damage In Developing Brain- A Protective Role For The Insulin-like Growth Factor System
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children ....The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children with diabetes are also at risk, when their therapy with insulin may at times be excessive, leading to hypoglycaemia and impaired glucose availability for the brain. This proposal is examining at the cellular level the mechanisms involved in loss of brain cells in the face of glucose starvation in these various conditions. We are using several in vitro models where we can grow segments of developing mouse brain or human nerve cells in a dish, compared to studies with mice subjected to low blood glucose (hypoglycemia). After establishing that our laboratory models are representative of the whole animal, we will explore the cellular mechanisms involved in neuronal death following hypoglycaemia, particularly the interaction between the insulin-like growth factor (IGF) and other cell survival genes. We will also examine the possibility that treatment with IGF will reduce the loss of nerves in the brain after an episode of hypoglycemia. This may offer new and effective early treatment for this damaging brain injury in both newborn babies and children with insulin-dependent diabetes.Read moreRead less
The Effect Of Alteration Of Glucose Use On Brain Function
Funder
National Health and Medical Research Council
Funding Amount
$131,731.00
Summary
Glucose has long been accepted as the mandatory fuel for the brain although it is not fully understood why this is so. Impairment of the glucose supply to the brain results in impairment in brain functions, coma and ultimately death. As a result the body possesses rigid regulatory systems to maintain blood glucose levels within set limits. In certain conditions where blood glucose levels frequently drop below normal, the brain compensates by increasing the uptake of glucose into the brain thus k ....Glucose has long been accepted as the mandatory fuel for the brain although it is not fully understood why this is so. Impairment of the glucose supply to the brain results in impairment in brain functions, coma and ultimately death. As a result the body possesses rigid regulatory systems to maintain blood glucose levels within set limits. In certain conditions where blood glucose levels frequently drop below normal, the brain compensates by increasing the uptake of glucose into the brain thus keeping the glucose supply normal despite lower than normal blood glucose concentrations. In these conditions, which include diabetic hypoglycaemia unawareness, anorexia and starvation, the normal hormonal systems warning of low blood glucose are bypassed. However, despite normal glucose supply to the brain, the performance of the brain is still adversely affected. The electrical activity of the brain changes, reaction times slow, and vigilance is decreased. This implies that, despite the brain having a normal supply of glucose, the glucose is being used differently and that these differences affect the functional performance of the brain. The AIMS of this study are to determine: 1. How does the use of glucose vary in the hypoglycaemia unawareness state? 2. How do these variations effect the performance of the brain? The SIGNIFICANCE of this work lies in 1. Increasing our understanding of the role of glucose in the brain, 2. Increasing our understanding of how the brain works, and, 3. Increasing our understanding of why cognitive impairment occurs in disorders such as diabetes, anorexia and starvation and whether this impairment is reversible. 4. Developing application of a relatively new technique, functional magnetic resonance spectroscopy, for use study of biochemical and cognitive brain disorders.Read moreRead less
Antenatal Insulin-like Growth Factor-I And Perinatal Growth, Survival And Function Of The Growth Restricted Fetus.
Funder
National Health and Medical Research Council
Funding Amount
$150,370.00
Summary
Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUG ....Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUGR in Australia in non-Aboriginal communities and between 7 to 17% in Aboriginal communities. Despite these adverse consequences for health of the individual throughout life, we do not currently have any effective therapies to treat IUGR. Small infants are mostly a result of an inadequate supply of oxygen and nutrients before birth, due to an impaired capacity of the mother to acquire these for the placenta to deliver them to the growing fetus or due to poor functioning of the placenta itself. This intrauterine malnutrition not only slows growth, but impairs the development of a range of body functions leading to the increased risk of illness and death in IUGR. Therapies to be used before birth to treat IUGR need to either restore supply of oxygen and nutrients or to promote growth and functional development. We have discovered that administration of a major growth promoting hormone, insulin-like growth factor-I (IGF-I), to the IUGR fetus, which has low levels of IGF-I, increases its growth. This project will therefore determine if directly giving this hormone in the IUGR fetus will restore development as well as growth before birth, improving function and hence survival and health after birth. If successful, the first effective approach to the antenatal treatment of IUGR will have been identified and would provide the essential knowledge for the design of a range of therapies to best restore the abundance of IGF within the IUGR fetus to improve perinatal and later outcomes.Read moreRead less