Obestatin is a 23-amino acid peptide hormone that is formed by cleavage of the ghrelin and obestatin prepropeptide. It is secreted by rat stomach, brain, perinatal pancreas, myenteric plexus, Leydig cells, and gastrointestinal mucosa and levels are decreased in rat plasma in response to fasting. Total obestatin levels are also reduced in rat fundus and intestine following treadmill exercise training. Obestatin inhibits release of insulin, somatostatin, and pancreatic polypeptide and stimulates glucagon release from mouse and rat pancreatic islets in vitro in a concentration-dependent manner. In vivo, obestatin (320 μg/kg) reduces food intake without affecting growth hormone or corticosterone release in mice. It also inhibits water intake and dehydration-induced vasopressin secretion in response to a hypovolemic challenge in rats.