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Prorenin And The Prorenin Receptor In Diabetic Retinopathy: Involvement Of The Wnt Pathway And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$580,042.00
Summary
Diabetic retinopathy is the leading cause of blindness in people of working age. The World Health Organization predicts that by 2030 more than 300 million people will have diabetes. Given the prevalence of diabetic retinopathy and the lack of effective treatments, there is an urgent need to identify the factors that contribute to its development. This project will determine the role of components of a hormonal system, prorenin and its receptor, in diabetic retinopathy and whether they are new ta ....Diabetic retinopathy is the leading cause of blindness in people of working age. The World Health Organization predicts that by 2030 more than 300 million people will have diabetes. Given the prevalence of diabetic retinopathy and the lack of effective treatments, there is an urgent need to identify the factors that contribute to its development. This project will determine the role of components of a hormonal system, prorenin and its receptor, in diabetic retinopathy and whether they are new targets for its treatment.Read moreRead less
The Role Of The Osteoblast In Mediating Glucocorticoid-Induced Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$825,254.00
Summary
Glucocorticoids (GC) exceed most other drugs in terms of numbers of patients treated and indications. Preventing or attenuating the deleterious effects of GC on fuel metabolism is therefore of great clinical significance. Our studies will create new knowledge regarding the mechanisms of GC-induced diabetes and osteoporosis, and will contribute to the development of new approaches that are essential to tackle the pressing medical problem of GC-induced disease.
Interactions Between Vasoactive, Epigenetic And Immunogenic Pathways In The Development Of Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
In our community, diabetic retinopathy is the leading cause of vision loss in people of working age. As the prevalence of diabetic retinopathy increases, there is an urgent need to understand the factors that cause its development in order to develop new treatments. This proposal will explore the contribution of hormones, the memory of retinal cells to high glucose and stress, and the immune system to diabetic retinopathy. The goal is to develop new and improved treatments for Australians.
Fenofibrate And Microvascular Events In Type 1 Diabetes (FAME 1) Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,883,529.00
Summary
Diabetes is one of the commonest cause of blindness in adults. Vision loss, which is irreversible, is a most feared complication of diabetes. A blood fat lowering drug called fenofibrate, available in Australia, has been shown to reduce eye damage in people with Type 2 diabetes by 35-40%, and to prevent eye damage in Type 1 diabetic animal models. This study will evaluate the potential benefits of fenofibrate in 450 adults with Type 1 diabetes who have early diabetic eye damage.
The Role Of Specific Nox Isoforms In Diabetic Renal Disease And Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$460,396.00
Summary
Diabetes is increasing worldwide and in Australia. The majority of patients with diabetes eventually will develop kidney disease and will die of blood vessel complications such as heart attacks and stroke. Oxidative stress (the generation of free oxygen radicals that react quickly with other proteins in the body causing tissue damage) has been suggested to play an important role in kidney and blood vessel disease observed in diabetic patients. This proposal will try to identify and measure speci ....Diabetes is increasing worldwide and in Australia. The majority of patients with diabetes eventually will develop kidney disease and will die of blood vessel complications such as heart attacks and stroke. Oxidative stress (the generation of free oxygen radicals that react quickly with other proteins in the body causing tissue damage) has been suggested to play an important role in kidney and blood vessel disease observed in diabetic patients. This proposal will try to identify and measure specific proteins in the kidney and vessels that are involved in the production of oxidative stress. We aim to define which one of these proteins is the most important. We will assess in detail how these proteins work and which other factors are activated leading to tissue damage. The ultimate goal of these studies is to find new treatment options to decrease the production of harmful molecules in the kidney and blood vessel wall thereby reducing kidney failure, heart attacks, stroke and gangrene in diabetes. In our studies, we will use medications already used in patients to treat high blood pressure in diabetes. In preliminary studies we have shown that these drugs also reduce oxidative stress. Furthermore, we will use novel, more specific treatments that the harmful ptoteins. Through a collaboration with Professor Harald Schmidt and his group from Germany who have recently moved to Monash University in Melbourne we will have access to mice in which specific genes for harmful proteins have been knocked out. These mice when made diabetic will most likely develop less or no kidney and blood vessel damage. Our studies will help to identify the most important oxidative stress producing protein associated with kidney and vessel disease. This knowledge will lead to more effective and more potent treatments for patients with diabetes to prevent, stop or even improve kidney and blood vessel disease thereby reducing disability and death in this high risk group of patients.Read moreRead less
Omega 3 Polyunsaturated Fatty Acid Analogues In The Treatment Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$418,446.00
Summary
Treatment of diabetes has become an even greater challenge to our community today. The ill health from diabetes arises from the high blood sugar levels. Treatment of diabetic complications such as kidney damage has now become a major goal. This research addresses this problem by trying to find out if a group of novel polyunsaturated fatty acids can target the process initiated by high blood sugar responsible for kidney damage.
Hepatic Oxidative Stress, PTPs & STAT Signalling In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$1,086,547.00
Summary
Obesity is increasing at an alarming rate worldwide and is a leading cause of morbidity and mortality. Obesity is causally linked to the development of insulin resistance, a prelude to type 2 diabetes. In this proposal we will define a novel liver centric mechanism by which insulin resistance and oxidative stress may promote the development of morbid obesity, type 2 diabetes and liver disease.
The Nuclear Growth Hormone Receptor- Its Actions And Mechanism Of Nuclear Translocation
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
We and others have found that cell surface receptors for growth factors such as EGF, FGF and growth hormone can be found in the nucleus of proliferating cells. We have shown that many cancers have elevated nuclear GH receptor including leukemia, breast and colon cancer. If we artificially target the GH receptor to the nucleus, the resulting cells are tumorigenic when injected into immunocompromised mice, rapidly form ing metastasising tumours. To create more effective inhibitors of this tumourog ....We and others have found that cell surface receptors for growth factors such as EGF, FGF and growth hormone can be found in the nucleus of proliferating cells. We have shown that many cancers have elevated nuclear GH receptor including leukemia, breast and colon cancer. If we artificially target the GH receptor to the nucleus, the resulting cells are tumorigenic when injected into immunocompromised mice, rapidly form ing metastasising tumours. To create more effective inhibitors of this tumourogenesis, and to define the physiological roles of nuclear GH receptor, we will define the transport process which carries the receptor to the nucleus and block it. We will also seek to define how the receptor in the nucleus interacts directly with DNA to inhibit programmed cell death. To carry out these projects we will use sophisticated proteomics -mass spectrometry to identify the proteins interacting with the receptor in the transport and gene activation processes. The role of candidates will be tested by preventing their expression or by direct inhibition of their action using drugs or dominant negative versions. These approaches will provide leads to new anti-cancer therapeutics, and therapies for blocking diabetic blindness and kidney failure.Read moreRead less