Role And Mechanism Of Connective Tissue Growth Factor In Diabetic Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$382,820.00
Summary
Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen pa ....Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen patient outcomes. We have generated data in experimental diabetes in rodents that strongly implicates a heart growth factor in causing diabetic cardiomyopathy. This protein, called connective tissue growth factor (CTGF), is increased in diabetic cardiomyopathy, and is elevated by high glucose and other factors in diabetes. We have published data showing that CTGF causes tissue scarring like that which occurs in cardiomyopathy, by affecting signals in cells called fibroblasts. It increases the laying down of extracellular matrix (ECM) and also inhibits the degradation of ECM by the proteins that break down matrix, known as the MMPand PAI systems. Such accumulation of ECM is thought to be a major factor leading to abnormal muscle function in cardiomyopathy. We now plan to block CTGF in this diabetic heart model to determine if we can prevent diabetic cardiomyopathy. We have generated two methods to inhibit CTGF in the animal model. Echocardiography (a heart ultrasound test), and molecular analysis of the heart tissue will determine if we can prevent the otherwise adverse functional and structural changes of diabetes in the heart. We will also study our baboon model of diabetes to determine if diabetic cardiomyopathy with increased heart CTGF is present in the primates. Cell culture studies from rat heart fibroblasts and myocytes will determine how CTGF has the effect on cells to cause cardiomyopathy and how we might further prevent this condition developing in diabetes.Read moreRead less
Non-alcoholic steato-hepatitis (NASH) is a common disease of liver inflammation and scarring, which may progress to cirrhosis or liver cancer. While type 2 diabetes causes a higher rate of NASH and more rapid NASH progression the reasons for this are not clear. We have developed a novel animal model of NASH with diabetes added to dietary induced obesity. We show that a growth factor is elevated in the affected livers. We plan to block the growth factor to see if we can prevent NASH worsening.
Diabetic cardiomyopathy (DiabCM) is common in people with diabetes. It predisposes to heat failure. Its cause remains unclear and there is no specific treatment for DiabCM. Inflammation is a fundamental tissue response to a metabolic insult and it occur in DiabCM. The central hypothesis in this work is that inflammation through myocardial macrophage cells contributes to DiabCM. This hypothesis will be tested in animal models and also in cell culutre studies.
How Intra-abdominal Transplantation Of Subcutaneous Adipose Tissue Prevents High-fat Diet-induced Insulin Resistance And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$358,465.00
Summary
In obese humans, storing excess fat within the abdomen is associated with the development of adult-onset diabetes and cardiovascular disease. However, the mechanisms linking intra-abdominal fat accumulation with these diseases are not well understood. We have studied intra-abdominal fat accumulation in mice using a transplant model, and we have found that transplanting subcutaneous fat intra-abdominally prevents diet-induced obesity and glucose intolerance. We aim to investigate the underlying m ....In obese humans, storing excess fat within the abdomen is associated with the development of adult-onset diabetes and cardiovascular disease. However, the mechanisms linking intra-abdominal fat accumulation with these diseases are not well understood. We have studied intra-abdominal fat accumulation in mice using a transplant model, and we have found that transplanting subcutaneous fat intra-abdominally prevents diet-induced obesity and glucose intolerance. We aim to investigate the underlying mechanisms.Read moreRead less
The effects of therapeutic glucocorticoid doses on carbohydrate and energy metabolism and cardiovascular risk have not been fully clarified. This PhD thesis will be based around two studies aiming to: 1.) Define mechanisms underlying the adverse effects of low dose prednisolone in patients with inflammatory rheumatologic disease and 2.) Improve treatment of prednisolone-induced hyperglycaemia in hospitalized patients.
Thyroid-sympathoadrenal Regulation Of Human Brown Fat
Funder
National Health and Medical Research Council
Funding Amount
$447,141.00
Summary
This project aims to determine how hormones influence the growth and activity of brown fat in humans. Majority of fat cells in the body are white fat cells, which store fat, and cause obesity when in excess. Brown fat cells function like generators. They burn fat and release energy as heat. Humans with lots of brown fat are lean. What controls brown fat activity is currently unknown in humans. This project investigates how hormones influence brown fat activity and may shed light on the therapeut ....This project aims to determine how hormones influence the growth and activity of brown fat in humans. Majority of fat cells in the body are white fat cells, which store fat, and cause obesity when in excess. Brown fat cells function like generators. They burn fat and release energy as heat. Humans with lots of brown fat are lean. What controls brown fat activity is currently unknown in humans. This project investigates how hormones influence brown fat activity and may shed light on the therapeutic potential of brown fat in obesity treatment.Read moreRead less