Activation Of HSP70: A Therapeutic Target To Treat Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$467,720.00
Summary
Type 2 diabetes is a prevalent and serious disease and the development of new strategies to treat it is warranted. In recent experiments we have been able to show that by upregulating a particular protein, referred to as a heat shock protein, we can reduce the clinical markers of type 2 diabetes by reducing key inflammatory pathways known to lead to insulin resistance. In this series of studies we will investigate whether activation of this protein is a target for therapeutic treatment.
VULNERABILITY OF THE INTRAUTERINE GROWTH RESTRICTED HEART AND KIDNEY TO ELEVATIONS IN BLOOD GLUCOSE LEVELS IN ADULTHOOD
Funder
National Health and Medical Research Council
Funding Amount
$58,288.00
Summary
It is proposed that the hearts and kidneys of subjects that were born small for gestational age are particularly vulnerable to the pathophysiological changes induced by hyperglycemia, even when blood glucose levels are only mildly elevated. In the present project, this concept will be investigated. The outcomes of this study will be particularly relevant to the Australian Aboriginal population, as they have a higher incidence than normal of low birth weight and impaired glucose metabolism.
Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their ....Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their etiology, both forms result in an inability of the body to control blood sugar levels. Beta cells release the hormone insulin, which regulates blood sugar levels. Current knowledge suggests that a loss of beta cell mass is important for both diseases. For type I diabetes the beta cells are destroyed by the immune system. Though for type 2 diabetes the causes are less clear, it is apparent that the beta cells are dying. Our research is focused on understanding the molecular pathways that control beta cell survival and regulate their death. Such knowledge would help us understand the complex processes leading to the development of diabetes. Furthermore, we could use this knowledge in the design of genetic engineering strategies to create 'death-defying' beta cells, as a potential therapeutic strategy for the treatment of diabetes.Read moreRead less
Analysis Of The Role Of Vesicle Docking/Fusion Proteins In Trafficking Of The Glut4 Glucose Transporter In Adipocytes
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
The objective of these studies is to understand the molecular mechanisms that are involved in the control of blood glucose levels by the hormone insulin. Elevated blood glucose levels following a meal stimulate the pancreas to release insulin into the circulation. Insulin acts to reduce blood sugar levels by stimulating the uptake of glucose into fat and muscle and suppressing glucose production by the liver. Defects in insulin action in these tissues are the primary cause of Type II diabetes. T ....The objective of these studies is to understand the molecular mechanisms that are involved in the control of blood glucose levels by the hormone insulin. Elevated blood glucose levels following a meal stimulate the pancreas to release insulin into the circulation. Insulin acts to reduce blood sugar levels by stimulating the uptake of glucose into fat and muscle and suppressing glucose production by the liver. Defects in insulin action in these tissues are the primary cause of Type II diabetes. The debilitating effects of Type II diabetes, the dramatic increase its incidence, and the expense of treating the symptoms of diabetic complications have lead to the realization that the disease represents a major health problem requiring substantial research and development efforts. The project will focus on insulin regulation of glucose uptake in fat cells. Insulin promotes glucose uptake into fat by activating an intracellular signaling pathway that triggers the translocation of a unique glucose transporter protein (Glut4) from storage sites inside the cell to the cell surface. Glut4 translocation is mediated by small membrane vesicles that function to sequester the glucose transporter inside cells in the absence of insulin, and to shuttle Glut4 to the cell surface in response to the hormone. Despite the central importance of this event to the maintenance of normal blood glucose levels, it is poorly understood. The studies will be directed towards investigating the cellular machinery involved in the latter stages of insulin-stimulated glucose uptake- the vesicle-mediated delivery of Glut4 to the cell surface. The objective of these studies is to better understand the molecular basis for Glut4 translocation, and regulation by the insulin signaling cascade. Accomplishment of this goal may suggest potential drug intervention strategies aimed at enhancing insulin-stimulated Glut4 translocation and promoting improved control of blood glucose levels in Type II diabetes.Read moreRead less
Obesity Induced By Chronic High-Energy Diet: Central Influences In Development And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$221,210.00
Summary
This project is about the study of central regulation of energy balance contributing to prevention or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and economically. Development of human obesity and its related metabolic disorders generally develops over a long period and eventually becomes a chroni ....This project is about the study of central regulation of energy balance contributing to prevention or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and economically. Development of human obesity and its related metabolic disorders generally develops over a long period and eventually becomes a chronic condition. Generally, chronic consumption of high-energy food in excess of expenditure leads to excessive fat accumulation and promotes the development of obesity. However, under these conditions, some individuals become obese, while others remain lean indicating that variation in susceptibility is an important determinant of the development of obesity. It is apparent that those individuals resistant to obesity have a more effective defence system against excessive fat accumulation. Using the animal models developed in our laboratory, the proposed research aims to search for the differences in the central regulation between the mice resistant or susceptible to the development of obesity. The outcomes we expect to achieve include: 1) better understanding of central factors controlling energy balance, 2) clarification of the central factors responsible for dysregulation of this system by chronic consumption of a high-energy diet, and 3) identification of those factors contributing to prevention against such dysregulation. Further, according to our previous study [XFH1, 2, 3], we propose to use the drugs targeting on the specific receptor subtypes to test reversibility of chronic high energy diet-induced obesity.Read moreRead less
Obesity: The Role Of Neuropeptide Y, Melanocortin And Serotonin Systems In Development And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
This project is about the study of central regulation of energy balance contributing to protection or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and financially. Development of human obesity and its related metabolic disorders is a long term process generally develops over a long period and event ....This project is about the study of central regulation of energy balance contributing to protection or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and financially. Development of human obesity and its related metabolic disorders is a long term process generally develops over a long period and eventually becomes a chronic condition. Generally, chronic consumption of high-energy food in excess of expenditure leads to excessive fat accumulation and promotes the development of obesity. However, studies on both humans and experimental animals have revealed that not all individuals become obese on a high-energy diet; thus, individual susceptibility is an important phenomenon allowing us to search for the genes contributing to the individuals' susceptibility or resistance to diet-induced obesity and to identify for effective targets for both prevention and treatment of obesity. Using the animal models developed in our laboratory, the proposed research aims to demonstrate the differences in the central regulation between the mice resistant or susceptible to the development of chronic high-energy diet-induced obesity. Outcomes of this project will provide us with: 1) better targets for the prevention of diet-induced obesity; (2) more effective treatments for the late stage of obesity and its related metabolic disorders; and (3) a better understanding of the individual susceptibility to diet-induced obesity.Read moreRead less