Glucagon-like Peptide-1 in Fishes: The Liver and Beyond

The incretin hormone glucagon-like peptide-1 (GLP-1), coencodedand expressed in the proglucagon gene in intestine and endocrinepancreas of all vertebrates, is an important regulator of insulinsecretion in the postprandial state of mammals. Additionally,the hormone acts in concert with insulin to remove glucose fromthe plasma. In mammalian B cells, lung, intestine and brain,GLP-1 receptors activate the adenylyl cyclase/cAMP system ofmessage transduction, with ancillary involvement of calciumand inositoltrisphosphate. While the peptide is fairly conservedin vertebrates, the fishes show dramatic biochemical and physiologicaldifferences to the situation in mammals and an incretin functionin fishes is questionable. Fish GLP-1 acts preferentially onthe liver, and recently enterocytes and brain membranes havebeen shown to be potential targets. GLP-1 actions generallyoppose those of insulin and supplant or supplement those ofglucagon by activating glycogenolysis, gluconeogenesis and lipolysisin liver and by accelerating glucose transport and curtailingglucose oxidation in enterocytes. In brain and enterocytes,GLP-1 targets adenylyl cyclase, while in the liver adenylylcyclase and cAMP play subordinate roles only. Although phospholipaseC had been implicated in GLP-1 action, the prevalent route ofmessage transduction in fish liver needs to be elucidated. Theunique functional switch of GLP-1 from a hyperglycemic hormonein fish to a glucostatic incretin in mammals remains a matterof conjecture.