The Role Of Liver Fructose-1,6-phosphatase (FBPase) In Body Weight Regulation
Funder
National Health and Medical Research Council
Funding Amount
$494,718.00
Summary
We have shown that fructose-1,6-bisphosphatase (FBPase), an enzyme important in producing sugar from the liver and one that is connected to Type 2 diabetes, does not cause an increase in sugar production when there is more of the enzyme in mouse livers. It does, however, lower both body weight and the amount of food the mice consume. We therefore hypothesise that liver FBPase is important in controlling body weight in humans and our project aims to find out exactly how and why this happens.
The Role Fructose-1,6-bisphosphatase On The Regulation Of Hepatic Gluconeogenesis
Funder
National Health and Medical Research Council
Funding Amount
$212,485.00
Summary
Type 2 or adult onset diabetes is a disease characterised by high blood sugar that causes damage to the kidneys, eyes and to the circulation and many patients die from heart attack or stroke. There is an increase in the prevalence of diabetes in Australia and a substantial portion of the health budget is utilised by caring for people with diabetes. Determining what exactly causes the increase in blood sugar levels is critical in the treatment of the disease. It is known that the sugar produced a ....Type 2 or adult onset diabetes is a disease characterised by high blood sugar that causes damage to the kidneys, eyes and to the circulation and many patients die from heart attack or stroke. There is an increase in the prevalence of diabetes in Australia and a substantial portion of the health budget is utilised by caring for people with diabetes. Determining what exactly causes the increase in blood sugar levels is critical in the treatment of the disease. It is known that the sugar produced and released by the liver is an important contributor to the high blood sugar levels found in patients with diabetes. The main biochemical pathway responsible for this is called gluconeogenesis, a complex arrangement of enzymes, which convert amino acids and fat into sugar. Although it is known that this pathway is overactive in patients with diabetes, the exact reason for this is not clearly understood. The aim of this proposal is to produce a transgenic mouse that has an increase in liver sugar production as a result of an increase in gluconeogenesis, and to study its effects on blood sugar levels. Furthermore, studies will be performed to understand the regulation of this pathway by infusing the transgenic mice with insulin, the hormone that inhibits gluconeogenesis. The mechanism of action of insulin will be determined by the measurement of key enzymes that regulate gluconeogenesis. The significance of this grant is to identify possible sites for the development of new drugs or gene therapy that will lead to a decrease in the production of sugar by the liver. This will lead to better control of blood sugar levels and slow down or even prevent the onset of diabetes complications.Read moreRead less
Mechanisms Of Insulin Resistance And Diabetes Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$633,783.00
Summary
The two main forms of diabetes - types 1 (T1D) and 2 (T2D) - pose a major problem. It is difficult to identify what causes diabetes. Recently, people at risk of T1D were found to have insulin resistance, a condition thought typical only of T2D. Excitingly, we discovered that the best T1D animal model also shows insulin resistance, and we used it to map important genes. We will now identify these genes. This will help us understand the disease process and to develop better treatments for it.
Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. Although there are currently therapies to reduce bone loss, no current treatment effectively reconstructs lost bone. In this project, which is designed to identify new genes that may in the future be targeted by drugs to reverse osteoporosis, we have identified specific sets of genes that appear to work together to increase bone formation. This ....Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. Although there are currently therapies to reduce bone loss, no current treatment effectively reconstructs lost bone. In this project, which is designed to identify new genes that may in the future be targeted by drugs to reverse osteoporosis, we have identified specific sets of genes that appear to work together to increase bone formation. This proposal is aimed at characterising these genes and the ways in which they work to determine whether they may be good targets for new osteoporosis treatments. We will examine the patterns of these genes in bone. We will also use cell cultures in which bone forming cells develop and function, to determine when the genes are expressed and how they function. We will test the ability of the candidate genes to cause an increase in the amount of bone forming activity in these cell cultures. An increase in bone formation may be caused by an increase in the number bone-forming cells, an increase in the activity of the cells, a decrease in cell death, or a combination of these changes. Each possibility will be tested. This research is important because of the need for new osteoporosis therapies to repair weakened bones. The knowledge resulting from this proposal has the potential to provide an important contribution to skeletal health and thus aged health worldwide.Read moreRead less
The Pathogenesis Of Motor Neuron Degeneration Caused By A Triplet Repeat Expansion In The Androgen Receptor Gene.
Funder
National Health and Medical Research Council
Funding Amount
$284,748.00
Summary
Male sex hormones, or androgens, work by binding to a specific receptor, known as the androgen receptor. Androgens have an important and yet poorly understood role in nerve function. Our research is investigating how a genetic mutation in the androgen receptor causes Kennedy?s disease. This is a rare disease, affecting adult males, which causes nerves to die. The nerves which are affected are those supplying our muscles, called motor neurons. This leads to muscle wasting in the face and body. Ot ....Male sex hormones, or androgens, work by binding to a specific receptor, known as the androgen receptor. Androgens have an important and yet poorly understood role in nerve function. Our research is investigating how a genetic mutation in the androgen receptor causes Kennedy?s disease. This is a rare disease, affecting adult males, which causes nerves to die. The nerves which are affected are those supplying our muscles, called motor neurons. This leads to muscle wasting in the face and body. Other symptoms include testicular wasting, reduced fertility and breast tissue enlargement. It is currently not known what causes motor nerves to degenerate in Kennedy?s disease. We are endeavouring to investigate the cause of Kennedy?s disease via the generation of a transgenic mouse carrying this mutation. It is only through a studying transgenic mouse affected by this disease can we begin to understand what is happening to nerves to cause them to die, and importantly, how can we prevent them from dying. These studies will also provide crucial information on the effects of sex hormones on nerves. As there is currently no treatment for Kennedy?s disease, an aim of this project is to investigate how we can treat this disease. This will be the first time that we can systemically test potential treatments and work toward preventing the degeneration of these nerves. Kennedy?s disease is related to a number of other neurodegenerative diseases including Huntington?s disease, which are caused by similar genetic mutations. All of these diseases are caused by degeneration of specific nerve cells. Evidence suggests that there may be similar mechanisms involved in all of these diseases. The results of this study will therefore help us to understand a range of diseases and may eventually lead to the development of therapeutic strategies to prevent their debilitating effects.Read moreRead less