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
TRAFFICKING OF METABOLITES BETWEEN M LLER CELLS AND NEURONS IN DIABETIC RETINOPATHY.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Diabetes is the leading cause of blindness in the working population. In some diabetics, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an incease in growth factors from cells in the retina called Muller cells. Muller cells are vital for the normal function of the retina, and a ....Diabetes is the leading cause of blindness in the working population. In some diabetics, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an incease in growth factors from cells in the retina called Muller cells. Muller cells are vital for the normal function of the retina, and are known to be abnromal late in diabetes. They may also be dysfunctional early in diabetes and could play a significant role in the early chnages seen in diabetes. Therefore a good understanding of how Muller cells change and the time at which they change is vitally important to gain a better undetrstanding of the defects that are associated with diabetes. Furthermore, an understanding of the basic underlying cellular changes that occur in diabetes will aid the development of more specific therapeutic agents in the future.Read moreRead less
Muller Cell Reactivity During Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
Diabetes is the leading cause of blindness in the working population. In some patients with diabetes, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an increase in growth factors from cells within the retina called Muller cells. Muller cells are vital for the normal function of ....Diabetes is the leading cause of blindness in the working population. In some patients with diabetes, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an increase in growth factors from cells within the retina called Muller cells. Muller cells are vital for the normal function of the retina and are known to be abnormal late in diabetes. They may also be dysfunctional early in diabetes and could play a significant role in causing the early changes seen in diabetes. Therefore a good understanding of how Muller cells change and the time at which they change is vitally important to gain a better understanding of the defects that are associated with diabetes. Furthermore, an understanding of the basic underlying cellular changes that occur in dibaetes will aid the development of more specific therapeutic agents in the future.Read moreRead less
Structural And Drug Discovery Studies Of Oxidative Stress Regulator, Thioredoxin-interacting Protein
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Toxic oxygen molecules known as Reactive Oxygen Species (ROS) are by-product of normal metabolism. The excess of ROS is damaging and is well known to contribute to ageing process and age-related diseases such as cancer, diabetic complications, immune-system decline, and cardiovascular conditions to name a few. The human body possesses several defense systems that protect us from the excess of ROS maintaining a healthy level of ROS. A down-regulator of one of this systems, a protein called TXNIP, ....Toxic oxygen molecules known as Reactive Oxygen Species (ROS) are by-product of normal metabolism. The excess of ROS is damaging and is well known to contribute to ageing process and age-related diseases such as cancer, diabetic complications, immune-system decline, and cardiovascular conditions to name a few. The human body possesses several defense systems that protect us from the excess of ROS maintaining a healthy level of ROS. A down-regulator of one of this systems, a protein called TXNIP, has been recently discovered. The amount of TXNIP is increased in such conditions as high glucose, a first sign of diabetes, and under ischemia, a shortage of blood supply occurring during heart attack. This weakens the anti-oxidant defense systems and makes the organism more vulnerable to ROS exposure. Our team of researchers embarked on structural and functional studies of TXNIP with the purpose to identify small molecules that can interfere with the undesirable action of TXNIP. These molecules might become useful therapeutic agents to counteract weakening organism's ROS defense system caused by TXNIP in many disease conditions such as, cancer, diabetes and cardiac failure.Read moreRead less
The Adverse Effects Of Diabetes On Stroke: An Echoplanar MRI Study
Funder
National Health and Medical Research Council
Funding Amount
$278,418.00
Summary
Stroke is the most common, major brain disease in Australia. It is the third most common cause of death and the most common cause of adult disability. There is a close link between diabetes and stroke. Firstly, diabetes is an important risk factor for the development of stroke. Secondly, about one third of stroke patients have diabetes. In general, their outcome is much worse than other patients. In fact little is known about the cause of this adverse effect in stroke patients and there is uncer ....Stroke is the most common, major brain disease in Australia. It is the third most common cause of death and the most common cause of adult disability. There is a close link between diabetes and stroke. Firstly, diabetes is an important risk factor for the development of stroke. Secondly, about one third of stroke patients have diabetes. In general, their outcome is much worse than other patients. In fact little is known about the cause of this adverse effect in stroke patients and there is uncertainty whether intensive control of blood sugar in acute stroke improves outcome. Our pilot work suggests that raised brain lactate, together with larger stroke size, might together be responsible for the worse outcome in diabetic patients. We can now measure brain lactate and stroke size with new MRI techniques called echoplanar MRI, which can allow measurements of brain chemistry, blood flow, potentially viable and dead tissue. A new monitoring device allows non-invasive measurement of blood sugar every 5 minutes. Using these strategies, we are planning a comprehensive study of the causes of the worse stroke outcome with diabetes. In addition, we are incorporating a study to determine whether intensive control of blood sugar in the first 3 days after stroke, compared with standard treatment, reduces brain lactate and growth of the actual stroke. An understanding of these effects will have important implications for the acute treatment of stroke patients. If we can show that rigorous control of blood sugar reduces brain lactate and stroke growth, our study will lay the ground work for a large clinical trial. This could have important implications, both in Australia, and overseas.Read moreRead less
My research focuses on the mechanisms responsible for diabetic kidney and heart complications with an emphasis on identifying novel targets as the basis for developing new treatment to reduce the burden of these complications. It is hypothesised that diabetic complications arise as a result of a number of key factors, the most important being chronic elevation of blood glucose.
Characterisation Of Novel AGE Binding Proteins: Implications For Diabetic Vascular Complications.
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This i ....This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This is a highly novel finding which now needs to be examined in more detail. The ERM proteins which include ezrin, radixin and moiesin are found at many sites of diabetic complications including the kidney, retina and blood vessel wall. They have a number of functions including effects on cell adhesion and cell structure. This is important in diabetes where changes in cells including altered structure have been observed. This grant will characterise the interactions between AGEs and ERM proteins at the molecular and cellular level. It will define how AGEs influence cells via interactions with ERM proteins. These studies have the potential to lead to treatments that may modulate the AGE-ERM interactions, thereby retarding or preventing diabetic vascular complications. These complications are of important clinical significance since they are the major cause of morbidity and mortality in the diabetic population. Furthermore, diabetes is a major cause of premature atherosclerosis in our community, diabetic kidney disease is the leading cause of end-stage renal failure in the Western world and diabetic retinopathy (eye disease) is the main cause of blindness in the working age population.Read moreRead less
E-PREDICE Early Prevention Of Diabetes Complications In Europe
Funder
National Health and Medical Research Council
Funding Amount
$917,400.00
Summary
The e-PREDICE study will randomise 3000 people aged 45-74 with mild hyperglycaemia or early diabetes to treatment with intensive lifestyle modification alone, or plus metformin, or sitagliptin, or liraglutide, aiming to reduce diabetes eye, kidney and nerve damage. The Australian arm will be co-ordinated by the University of Sydney and other sites include Baker IDI Heart and Diabetes Institute, Royal Melbourne Hospital, St Vincent’s Hospital Melbourne and Royal Brisbane and Womens Hospital