Abstract 11165: Activation of IGF-1/PI3/GSK-3ss Signaling Prevents High Glucose-induced Transition of Human Cardiac Progenitor Cells Into Fibroblasts

Background: Cardiac progenitor cells (CPC) can repair the myocardium injured by infarction. However, CPC may not function well under the diabetic condition. Exposure to high levels of glucose (HG) may induce cardiomyopathy and fibrosis in patients with diabetes. Signaling transduction via transforming growth factor-β (TGF-β) and its responding transcription factor, Snail, (TGF-β/Snail) is involved in fibrosis. Insulin-like growth factor (IGF-1) decreases TGF-β expression. Thus, it is important to investigate whether IGF-1 activation of the PI3 kinase/glycogen synthase kinase 3β (GSK-3β) signaling pathway prevents HG-induced transition of CPC to fibroblasts. Methods and Results: Human CPC were isolated and cultured from normal human heart tissue. They were exposed to different concentrations of glucose. Compared to CPCs incubated in normal glucose (NG) (5 mM), CPC incubated in HG (25 mM) showed increased TGF-β mRNA levels (3.1 ± 0.5 fold, p<0.05, n=4) and Snail (2.9 ± 0.4 fold, p<0.05, n=4) in a dose- and ...