Description
Exendin-4 is an analog of glucagon-like peptide 1 (GLP-1); it acts as an agonist at GLP-1 receptors. Exendin-4 exhibits cardioprotective, anti-inflammatory, and antioxidative activities. In mesangial cells, exendin-4 increases phosphorylation of AMPK and decreases phosphorylation of ERK, inhibiting fibronectin secretion and cell proliferation. In animal models of cardiac ischemia/reperfusion, exendin-4 decreases levels of high-mobility group box 1 (HMGB1), lactate dehydrogenase (LDH), creatine kinase, and malondialdehyde (MDA) and prevents decreases in superoxide dismutase (SOD) levels, decreasing infarct size. Additionally, this compound inhibits ox-LDL-induced migration of macrophages, increases in matrix metalloproteinase-9 (MMP9), and activation of NF-κB in vitro. In other cellular models, exendin-4 suppresses increases in ROS, activation of caspases, and release of cytochrome c, preventing oxidative damage and mitochondria-mediated apoptosis. Exendin-4 was originally found in Heloderma lizards. Like other GLP-1 agonists, this compound may exhibit anti-diabetic activity.