Role Of Advanced Glycated End Products In Mediating Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$414,000.00
Summary
Diabetes is on the increase in the Western world and with this increase comes the burden of increased complications. One of these is atherosclerosis which leads to heart attacks, strokes and gangrene. In this grant we consider the role of a biochemical reaction where sugar attaches to proteins called advanced glycation and how it may promote atherosclerosis. We will use novel drugs to block vessel damage in a model of diabetic mice prone to atherosclerosis. We will also inject these sugar-attach ....Diabetes is on the increase in the Western world and with this increase comes the burden of increased complications. One of these is atherosclerosis which leads to heart attacks, strokes and gangrene. In this grant we consider the role of a biochemical reaction where sugar attaches to proteins called advanced glycation and how it may promote atherosclerosis. We will use novel drugs to block vessel damage in a model of diabetic mice prone to atherosclerosis. We will also inject these sugar-attached proteins (AGEs) into mice to see how they directly influence the vessel wall. We will characterise molecular and cellular changes in response to these AGEs. These studies will ultimately lead to better treatments to prevent, slow down or reverse blood vessel damage in diabetes.Read moreRead less
The Role Of Insulin Hypersecretion In Beta Cell Dysfunction In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$318,622.00
Summary
The treatment of diabetes involves the use of drugs that stimulate the release of insulin from the pancreas to reduce the high blood sugar levels. However, we believe that while in the short term this is a good strategy, in the long-term it damages the cells that produce insulin leading to a worsening state of diabetes. It is the aim of this application to understand the mechanisms by which the insulin producing cells are damaged when forced to oversecrete insulin.
A Randomised Study Of Insulin/dextrose Infusion For Myocardial Infarction In Patients With Diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$181,018.00
Summary
In Australia, some 5-10% of the population have diabetes, and the prevalence is rising. Some 50% of diabetics over the age of 40 will die from cardiovascular disease, and the cardiac mortality amongst patients with diabetes is 3 times that of the general population. One quarter of patients admitted to hospital in Australia with myocardial infarction (heart attack) have diabetes. Myocardial infarction (AMI) is much more likely to be fatal for a person with diabetes, and the mortality rate after o ....In Australia, some 5-10% of the population have diabetes, and the prevalence is rising. Some 50% of diabetics over the age of 40 will die from cardiovascular disease, and the cardiac mortality amongst patients with diabetes is 3 times that of the general population. One quarter of patients admitted to hospital in Australia with myocardial infarction (heart attack) have diabetes. Myocardial infarction (AMI) is much more likely to be fatal for a person with diabetes, and the mortality rate after one year is about double that of the non-diabetic population. Whilst considerable advances have been made in recent years in reducing the mortality from AMI, there have been few studies with the specific aim of optimising management for patients with diabetes in this situation. One recent study (the DIGAMI Study) however, examined the use of insulin-dextrose infusion therapy at the time of AMI for patients with diabetes and found a significant reduction in mortality rate amongst treated patients. However, due to the design of the study, it is not possible to determine if it was the insulin-dextrose infusion which resulted in the reduced mortality, or if it was one of a number of confounding variables. Nonetheless, the DIGAMI Study has raised the possibility that insulin-dextrose infusion will improve the outcome for diabetics, and theoretically, there are good reasons that this may provide a real benefit, via a reduction in free fatty acids, which may potentiate damage to the heart. Our study aims to determine if insulin-dextrose infusion therapy improves the prognosis of diabetic subjects with AMI. This will be performed as a randomised controlled trial across 4 teaching hospitals. If its benefit are confirmed, then this will have significant implications for the management of diabetics with AMI, as insulin-dextrose infusions are not currently routine, especially for patients with lower levels of hyperglycaemia.Read moreRead less
Mechanisms Of Pro-atherogenic Effects Of Androgens In Human Vascular Cells
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Atherosclerosis is the most important cardiovascular disease and is now the leading cause of death in Western societies. A major clue to the causality of the disease is the striking gender gap in its prevalence and severity. The gender gap in atherosclerotic cardiovascular disease may be due to genetic, lifestyle or hormonal differences between males and females. Of these, hormonal differences are the most amenable to therapeutic intervention. Accordingly, there has been a lot of interest in the ....Atherosclerosis is the most important cardiovascular disease and is now the leading cause of death in Western societies. A major clue to the causality of the disease is the striking gender gap in its prevalence and severity. The gender gap in atherosclerotic cardiovascular disease may be due to genetic, lifestyle or hormonal differences between males and females. Of these, hormonal differences are the most amenable to therapeutic intervention. Accordingly, there has been a lot of interest in the potential protective effects of estrogens but few have studied the role of androgens with sophisticated approaches to androgen physiology and pharmacology. Clues from epidemiological and our recent studies suggest that androgenic influences on atherosclerosis may involve positive and negative effects on atherogenesis but the mechanisms are not understood. We now propose a comprehensive approach to studying androgenic effects on vascular biology both to enhance knowledge as well as potentially opening new therapeutic options in selective androgen receptor modulation.Read moreRead less
Defining Vascular Health And Modifiable Risk Factors Over Time In Childhood.
Funder
National Health and Medical Research Council
Funding Amount
$368,061.00
Summary
Adult heart disease and strokes have their origin in childhood. We will follow healthy children and children with diabetes or obesity over 2 years during puberty when blood vessel disease is detectable. We will define which are the most sensitive markers of blood vessel disease and the continuum of risk factors. This is essential knowledge to best define children at risk and to test clinical and public health interventions.
Reproduction is controlled by the brain through the hormone gonadotropin releasing hormone (GnRH). Leptin from fat acts on the brain to 'inform' GnRH cells of metabolic state; low levels signal lack of energy stores and suppress reproduction. Leptin treatment of lean individuals restores reproductive function, but the mechanism is not clear. Our data implicate the melanocortins as a means of transmitting information on metabolic state to GnRH cells and the project investigates this pathway.