The Relationship Between Non-Alcoholic Fatty Liver Disease And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Non alcoholic Fatty Liver Disease (NAFLD) threatens to become a major public health problem. Its increasing prevalence is associated with parallel increases in obesity and diabetes. This study aims to understand the mechanisms involved in progression to liver failure and liver cancer in the setting of diabetes and the impact of NAFLD on blood sugar levels and diabetes complications (esp. cardiovascular). Using a recently developed animal model of type 2 diabetes and fatty liver, it will better d ....Non alcoholic Fatty Liver Disease (NAFLD) threatens to become a major public health problem. Its increasing prevalence is associated with parallel increases in obesity and diabetes. This study aims to understand the mechanisms involved in progression to liver failure and liver cancer in the setting of diabetes and the impact of NAFLD on blood sugar levels and diabetes complications (esp. cardiovascular). Using a recently developed animal model of type 2 diabetes and fatty liver, it will better define a novel therapeutic agent.Read moreRead less
Role Of Islet ?-cell Failure In The Pathogenesis Of Non-alcoholic Steatohepatitis
Funder
National Health and Medical Research Council
Funding Amount
$560,111.00
Summary
Some people respond to obesity poorly developing diseases such as non-alcoholic steatohepatitis (NASH) and diabetes. Other people do not, safely storing the excess energy in non-abdominal fat. The applicants will study 2 obese strains of mice; one develops “adipose tissue restriction”, NASH and diabetes, the other does not. The hypothesis that failure of compensatory insulin secretion to over-nutrition is an upstream event causing adipose tissue restriction, followed by NASH, will be tested.
Identification Of Novel Genes Influencing Development Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$558,920.00
Summary
Type 2 diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individual's energy metabolism. The number of affected people with type 2 diabetes has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies are inadequate to control the increasing numbers of affected ind ....Type 2 diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individual's energy metabolism. The number of affected people with type 2 diabetes has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies are inadequate to control the increasing numbers of affected individuals. Unfortunately the cause of disease is poorly understood, although genetic factors are known to be important, in other words it runs in the family. This project proposes to identify some of these factors (genes) and how they contribute to the disease. Using molecular flags on the DNA (like DNA fingerprinting) we have previously found that a small region on chromosome 12 is likely to carry one or more of these disease genes. But there are over 100 genes in the region. To help choose the most likely candidates first for testing, we have developed an automated computer database searching program ranked the genes based on what is already known about them. We have also taken a large number of physiological measures in a large group of people. Some of these measures are controlled by the same chromosome 12 region - thus to improve our chances of finding the genes quickly we will look at those that change the most between people with diabetes and people without diabetes. In this project we shall investigate the 20 genes most likely affect diabetes based on changes in physiological measures and what is already known about them. A successful finding means we will know more about the mechanism of disease development and be able to better develop new therapies for treatment and prevention. If none of these genes are the culprit, we would continue examination of the next set of genes likely to be involved and so on until we are successful.Read moreRead less
Obesity is becoming more common in Australian adults and children, and is a major contributor to a number of diseases including type 2 diabetes, cardiovascular disease and some cancers. Current weight loss strategies using either lifestyle modification (diet and exercise) or drugs are relatively ineffective in the majority of obese individuals. This is partly due to the fact that we have an incomplete knowledge of the factors that regulate weight in humans. In laboratory studies we have shown th ....Obesity is becoming more common in Australian adults and children, and is a major contributor to a number of diseases including type 2 diabetes, cardiovascular disease and some cancers. Current weight loss strategies using either lifestyle modification (diet and exercise) or drugs are relatively ineffective in the majority of obese individuals. This is partly due to the fact that we have an incomplete knowledge of the factors that regulate weight in humans. In laboratory studies we have shown that human fat cell development can be dramatically accelerated by fibroblast growth factor-1 (FGF-1). This growth factor is produced by human endothelial cells, which are cells that line the blood vessels in fat tissue. When human fat cell precursors (preadipocytes) are cultured in the presence of FGF-1 the preadipocytes divide much more rapidly than normal and, additionally, then develop into mature fat cells much more rapidly than normal. These processes involved in development of new fat cells form the basis of fat tissue expansion in the body. The effect of FGF-1 on human fat cell development is far greater in magnitude than that of other known factors that promote fat cell growth. The aim of this project is to determine the actual biochemical pathways that mediate the effect of FGF-1 in promoting fat cell growth and development. Results obtained will provide insight into the cellular and molecular mechanisms regulating expansion of fat tissue mass in humans. Research aimed at identifying these underlying mechanisms, or at potentially contributing or exacerbating factors, is critically important in development of novel and more effective approaches to prevention and treatment of obesity.Read moreRead less
Central And Peripheral Actions Of Insulin For The Control Of Muscle Capillary Recruitment
Funder
National Health and Medical Research Council
Funding Amount
$433,973.00
Summary
Type 2 diabetes is on the increase world wide and reflects the ever-increasing incidence of obesity. Whereas the likely cause of type 2 diabetes includes low physical activity and high fat diet, the primary metabolic abnormality is likely to be muscle insulin resistance. The cause of this resistance is controversial, but may stem from microvascular dysfunction where muscle becomes poorly perfused and unresponsive to the action of insulin to recruit capillary flow. In this project we will further ....Type 2 diabetes is on the increase world wide and reflects the ever-increasing incidence of obesity. Whereas the likely cause of type 2 diabetes includes low physical activity and high fat diet, the primary metabolic abnormality is likely to be muscle insulin resistance. The cause of this resistance is controversial, but may stem from microvascular dysfunction where muscle becomes poorly perfused and unresponsive to the action of insulin to recruit capillary flow. In this project we will further extend our seminal discoveries that insulin mediates capillary recruitment under normal circumstances and that in various models of insulin resistance insulin's ability to increase the perfusion of muscle is markedly impaired. We will explore the hypothesis, that insulin controls microvascular perfusion of muscle by a central neural mechanism ending at terminal arterioles on the vasculature and endeavour to identify the details of this control. We will use in-house novel techniques for examining both the role of central control mechanisms involving the brain as well as peripheral mechanisms by local infusion of various agents likely to either enhance or block insulin's microvascular action. A positive outcome will enhance our understanding of insulin action and the insulin resistance that precedes type 2 diabetes. There is also the possible outcome that important clues will be obtained leading to new therapeutic agents that could be used to treat type 2 diabetes.Read moreRead less