Glucagon: from hepatic binding to metabolism in teleost fish

Abstract

Glucagon is hyperglycemic and lipolytic in teleost fishes. This mini review examines the signaling pathway from glucagon binding to physiological effects in the teleost liver using the available literature and suggesting areas where additional studies are required. Glucagon has been shown to bind to high- and low-affinity receptors on hepatocytes of American eels ( Anguilla rostrata) and brown bullheads ( Ictalurus nebulosus), but not on any salmonid studied to date. Binding leads to increases in cAMP and inositol 1,4,5-trisphosphate (IP 3), but the magnitude of these changes correlates poorly with increases in glucose production. Activation of adenylyl cyclase (ACase) and of phospholipase C (PLC) is apparently responsible for these changes in 2nd messengers. Although protein kinases A and C have been reported in fish hepatic tissues, studies are limited regarding the effects of glucagon on these kinases. Changes in glycogen phosphorylase, phosphofructokinase, pyruvate kinase and triacylglycerol lipase activities have been correlated with glucagon-induced alterations in metabolism in some species. Receptor sequence analysis and further evaluation of individual components of the glucagon signaling cascade will lead to better understanding of the evolutionary changes in this important hormone system.