The Role Of Angiotensin Converting Enzyme 2 In Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$453,144.00
Summary
Most heart attacks and strokes arise from narrowing of the arteries. This process is regulated by a number of hormonal pathways. One of the most important is the renin angiotensin system. Our group has demonstrated important changes in this pathway which play a pivotal role in regulating the development of atherosclerosis and its response to treatment. It is predicted that these studies will provide critical information to develop innovative treatment strategies for cardiovascular disease.
Epigenetic Determinants Of Nephropathy In Adults With Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$532,118.00
Summary
The prevention and successful management of diabetic complications are issues of utmost importance for the health of Australians. We hypothesize that epigenetic pathways partly determine why some individuals with diabetes develop complications of their disease, while others do not, despite a similar duration of diabetes, treatment intensity and mean glucose exposure.
JDRF/NHMRC Diabetes Complications Centre Of Research Excellence
Funder
National Health and Medical Research Council
Funding Amount
$2,607,291.00
Summary
Despite intensive intervention some individuals with type 1 diabetes develop complications. There remains an urgent need for means to identify patients at risk of complications and new targets and therapies for preventing, arresting, treating and reversing them. The primary objective of the Diabetes Complications Centre of Research Excellence (DC-CRE) is to translate novel experimental findings into preventive/treatment strategies for the management of diabetes and its complications.
RAGE And ACE2 Shedding As Therapeutic Targets In Diabetes And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,447.00
Summary
We have previously demonstrated the pivotal role of two shed proteins, Receptor for Advanced Glycation End-products (RAGE) and Angiotensin Converting Enzyme Receptor 2 (ACE2) in heart disease and diabetic complications. In this project, we will use a novel technologies to modify shedding of these proteins from the cell surface and alter their ability to cause disease.
The Role Of Dicarbonyl-derived AGEs And RAGE In Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$470,617.00
Summary
Based on our pilot data we postulate that glucose derived molecules such as methylglyoxal (MGO) have effects on inflammation and oxidative stress leading to accelerated atherosclerosis in diabetes. Our studies aim to identify novel treatments which block these effects thus leading to superior protection and prevention of atherosclerosis in diabetes.
Role Of Epigenomic Changes In Conferring Hyperglycemic Memory
Funder
National Health and Medical Research Council
Funding Amount
$636,146.00
Summary
The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment h ....The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment has returned glucose levels towards normal.Read moreRead less
Targeting The AGE-RAGE Axis In Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$542,859.00
Summary
Based on extensive preliminary data we porpose that the AGE intercation with RAGE plays an important role in diabetes associated atherosclerosis. We will perform studies using a soluble form of the receptor RAGE which will trap AGEs in the blood and tissues and thus prevent diabetes related blood vessel damage. Furthermore, we will investigate if RAGE receptor on inflammatory cells such as macrophages plays a pivotal role in blood vessel injury in diabetes.
Circulating Low -molecular Weight AGEs In The Development And Progression Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$297,523.00
Summary
High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific rec ....High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific receptors that promote the damage and scarring of tissue. Where the glucose concentration is high, AGEs accumulate much more quickly. This is one reason why patients with good sugar control do better than those who are unable to control their blood sugars. The importance of this AGE pathway is illustrated by the fact that blocking the formation of AGEs is able to prevent kidney damage in animals with diabetes. In addition, exposure to AGEs can cause diabetes-like changes in the absence of high sugars. Our laboratory is a world leader in the study of the advanced glycation and methods blocking this process. The research proposed will investigate circulating levels of AGEs in experimental animals and patients with diabetes, and correlate them with the development and progression of complications of diabetesRead moreRead less
Non-invasive Detection Of Hypoglycaemia In People With Diabetes Using Brain Wave Activity
Funder
National Health and Medical Research Council
Funding Amount
$330,447.00
Summary
Hypoglycaemia remains a major cause of morbidity and mortality in people with both type 1 diabetes and type 2 diabetes who require insulin therapy. Current treatments for nocturnal hypoglycaemia are usually ineffective. Combining brain wave recording and artificial intelligence, we will identify the changes that precipitate an episode of hypoglycaemia allowing the development of a non-invasive device to prevent or alleviate these fearful and potentially life-threatening events.
Targeting The Anti-angiogenic Factors Of Preeclampsia: Soluble Endoglin And SFlt1
Funder
National Health and Medical Research Council
Funding Amount
$447,024.00
Summary
Preeclampsia is a severe disease of pregnancy - the placenta releases toxins in to mum's bloodstream that circulate her body and damage her organs. As there are no efficacious treatments, clinicians are forced to deliver babies irrespective of gestation. Although the two toxins of preeclampsia have been identified, little is known about their regulation. This project aims to elucidate the regulation of these toxins and design therapeutics that can prevent their release in the clinic.