SMAD2 and diabetes mellitus: Additionally, rat cardiomyocytes treated with conditioned media obtained from human EAT from patients with diabetes vs. patients without diabetes demonstrate reductions in contractile dysfunction, decreased insulin-mediated Akt-Ser473-phosphorylation (activation of cell survival pathway) and elevations in SMAD2 phosphorylation/activation (a TGF-β pathway protein implicated in cardiomyocyte fibrosis) demonstrating how EAT can affect cardiomyocyte function and remodeling (Greulich et al., 2012).