Apelin-13 is an endogenous peptide that exhibits neuroprotective and pro-angiogenic activities. Apelin-13 binds apelin receptors (APJ receptors) that heterodimerize with bradykinin receptors; upon binding, this complex signals for increases in phosphorylation of eNOS, activation of PKC, and cellular proliferation. Apelin-13 is also involved in the regulation of water balance, food intake, nociception, and cardiovascular responses. In vivo and in vitro, apelin-13 increases myocardial glucose uptake and GLUT4 membrane translocation in an AMPK-dependent manner. In animal models of ischemia/reperfusion, apelin-13 decreases neurological deficits, infarct volume, and brain edema, and also downregulates expression of Bax and caspase 3 through activation of the PI3K/Akt signaling pathway. Additionally, apelin-13 promotes proliferation, migration, and tube formation in myocardial microvascular endothelial cells.