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 Ezrin-radixin-moesin Proteins, Novel Binding Proteins For Advanced Glycation Endproducts, In Kidney Cells
Funder
National Health and Medical Research Council
Funding Amount
$493,220.00
Summary
High glucose levels in diabetes react with proteins to form AGEs and it is thought that this reaction may lead to kidney damage, which is one of the complications of diabetes. However, how this damage occurs is not completely understood. Cells need to maintain their shape and position for an organ to stay healthy. We have shown that AGEs affect kidney cells by interacting with and disturbing the function of proteins that maintain cell shape. We now want to study how this occurs.
Screening For Abdominal Aortic Aneurysms: Long-term Outcome And Role Of Circulating Markers Of Glycation
Funder
National Health and Medical Research Council
Funding Amount
$140,497.00
Summary
The abdominal aorta may undergo dilatation resulting an aneurysm. Some aneurysms may rupture causing death. The risk of rupture increases once the diameter exceeds 5cm. The management is detection and surgery for large aneurysms. As most aneurysms are asymptomatic prior to rupture screening of men using ultrasound may save lives. The aims of this study are to assess the role of screening on mortality from aneurysms and to assess a new blood test which may help monitor aneurysms.
A Population-based Cohort Study Of Brain Ageing - Rates Of Brain Structural Change, Functional Effects, And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$1,323,361.00
Summary
This study will provide unique longitudinal Australian data on the effects and causes of brain aging in a population-based sample of older people. The results may assist in preventing dementia and falls, major public health problems in older Australians.
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.
Cytosolic Oxidative Disturbances As A Source Of Mitochondrial Dysfunction In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$505,786.00
Summary
There is a critical need to identify new therapies for the growing number of patients with diabetic kidney disease. Current medicines only retard progressive disease. Our studies investigate defects in the power houses of the cell, the mitochondria. These defects cause generation of toxic free oxygen radicals which eventually starve the cell of energy production. Therefore, reversal of mitochondrial defects in diabetic kidney disease may be a novel therapeutic target.
Role Of Circulating Advanced Glycation End Products (AGEs) In Diabetic Nephropathy: Effect Of Benfotiamine Intervention
Funder
National Health and Medical Research Council
Funding Amount
$465,000.00
Summary
Advanced glycation products (AGEs) are compounds formed by the addition of sugars to amino acids (the building blocks of proteins). The addition of sugars to proteins induces biological changes that have been implicated in the development of diabetic complications, especially diabetic kidney disease. AGEs are a diverse group of compounds and to date the exact role that specific AGEs play in the causation of diabetic kidney disease is still unclear. However, new methods are now available that all ....Advanced glycation products (AGEs) are compounds formed by the addition of sugars to amino acids (the building blocks of proteins). The addition of sugars to proteins induces biological changes that have been implicated in the development of diabetic complications, especially diabetic kidney disease. AGEs are a diverse group of compounds and to date the exact role that specific AGEs play in the causation of diabetic kidney disease is still unclear. However, new methods are now available that allow the comprehensive quantification of individual AGE levels in blood. Our study involves the comparison of AGE blood levels, as a group or as specific AGEs with markers of diabetic kidney disease such as albumin (protein) excretion in the urine and the rate that the kidney filters the blood to form urine (glomerular filtration rate). Benfotiamine is a thiamine (vitamin B1) derivative that has been shown to decrease the formation of AGEs and to prevent kidney disease in diabetic animals. The present clinical study will assess whether benfotiamine has similar effects on AGEs and kidney disease in patients with type 2 diabetes. If successful, this study has the potential to provide a new treatment strategy for diabetic kidney disease in humans.Read moreRead less
Restricting Dietary Advanced Glycation End Product Intake As A Potential Therapeutic Tool In Diabetic Nephropathy.
Funder
National Health and Medical Research Council
Funding Amount
$483,351.00
Summary
Kidney disease is a serious complication of diabetes and may occur as a result of a biochemical process known as advanced glycation. These advanced glycation end products (AGEs) accumulate in the kidney causing disruption of function. Due to modern food processing techniques, the Australian diet has a high AGE content. Over-eating foods which are high in AGEs may worsen diabetic kidney disease. This proposal will test the effects of dietary AGE restriction and overfeeding on kidney function.