© 2000 by The Society for Integrative and Comparative Biology
Glucagon-like Peptide-1 in Fishes: The Liver and Beyond1
1 Department of Biochemistry and Microbiology, University of Victoria, Victoria, Canada
The incretin hormone glucagon-like peptide-1 (GLP-1), coencoded and expressed in the proglucagon gene in intestine and endocrine pancreas of all vertebrates, is an important regulator of insulin secretion in the postprandial state of mammals. Additionally, the hormone acts in concert with insulin to remove glucose from the plasma. In mammalian B cells, lung, intestine and brain, GLP-1 receptors activate the adenylyl cyclase/cAMP system of message transduction, with ancillary involvement of calcium and inositoltrisphosphate. While the peptide is fairly conserved in vertebrates, the fishes show dramatic biochemical and physiological differences to the situation in mammals and an incretin function in fishes is questionable. Fish GLP-1 acts preferentially on the liver, and recently enterocytes and brain membranes have been shown to be potential targets. GLP-1 actions generally oppose those of insulin and supplant or supplement those of glucagon by activating glycogenolysis, gluconeogenesis and lipolysis in liver and by accelerating glucose transport and curtailing glucose oxidation in enterocytes. In brain and enterocytes, GLP-1 targets adenylyl cyclase, while in the liver adenylyl cyclase and cAMP play subordinate roles only. Although phospholipase C had been implicated in GLP-1 action, the prevalent route of message transduction in fish liver needs to be elucidated. The unique functional switch of GLP-1 from a hyperglycemic hormone in fish to a glucostatic incretin in mammals remains a matter of conjecture.