Hypothesised anti-fibrotic mechanisms activated in sitagliptin- or metformin-treated GK hearts.

In T2DM cardiac cells, two major components such as HF and HG can trigger pro-fibrotic molecules (i.e. fibronectin) through activation of specific mediators [TGFß1, CTGF, ROS and transcription factors (TF)]. This response may be primarily attenuated by the GLP-1- or metformin-induced insulinotropic effect. However, a direct anti-fibrotic action of GLP-1GLP-1RPPARδ or metforminAMPK may also occur. In addition, the GLP-1 truncated isoform [GLP-1(9-36)] may also conserve anti-fibrotic properties by a GLP-1R-dependent or independent way. R; unknown receptor.