Neuromedin U (NMU) is a neuropeptide first demonstrated to drive smooth muscle contraction. Translated as a 174 amino acid propeptide, NMU is cleaved to different lengths in different animals. It has diverse receptor-mediated roles in vivo, as it regulates feeding, vasoconstriction, nociception, and bone remodeling and contributes to obesity, cancer and septic shock. NMU-25 is the active form of NMU in humans. It binds with high affinity to receptors on human left ventricle and coronary artery (KDs = 0.26 and 0.11 nM, respectively), eliciting endothelium-independent vasoconstriction. NMU-25 also suppresses glucose-stimulated insulin secretion in human islets, and this effect is lost in NMU R165W mutants, resulting in early-onset obesity.