Regulating prosclerosing growth factors by incretin therapy in diabetic cardiomyopathy
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Growth factors induced by diabetes contribute to tissue fibrosis and dysfunction, in conditions such as diabetic cardiomyopathy, and there is preliminary evidence that the incretins (eg GLP-1) can down regulate these factors and thus prevent diabetes complications.
Increasingly, there is evidence that diabetes mellitus through elevated glucose and lipids, increases certain growth factors, which then contribute to tissue damage and loss of function. Diabetic cardiomyopathy is characterised by up-regulation of growth factors such as connective tissue growth factor. In contrast, some gut hormones that are relatively lacking in diabetes are the incretins, especially glucagon-like peptide-1 (GLP-1). GLP-1 administration has recently been shown to reduce diabetic cardiomyopathy incidence and severity in animal models, although it s mechanism of action has not been defined. We have preliminary evidence to indicate that GLP-1 may function by inhibiting myocardial CTGF bioactivity. The main aims of this work are thus: 1. to determine if GLP-1 therapy in STZ-diabetes in vivo can inhibit and reverse changes of diabetic cardiomyopathy; 2. to determine if myocardial CTGF is regulated in vivo and in vitro (in cardiac myocytes and fibroblasts) by GLP-1 3. to determine if GLP-1 blocks the bioactivity of CTGF on cardiac myocytes and fibroblasts in vitro, and its cellular mechanism of action in this process.
Animal models of diabetic cardiomyopathy and structural and dysfunctional change; continuous and primary myocardial cells (myocytes and fibroblasts) in culture. Molecular methods of over-expression (AAV) and inhibition (SiRNA).
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diabetes, diabetes complications, diabetic cardiomyopathy, Connective tissue growth factor, Growth Factors, incretins, GLP-1, Cardiovascular & respiratory diseases, Chronic diseases & ageing, Liver & hormonal disorders, Cell biology, Heart & circulation, Human body
The opportunity ID for this research opportunity is: 227