Glucagon-like Peptide-1 (GLP-1) and the Control of Glucose Metabolism in Mammals and Teleost Fish1

SYNOPSIS. Glucose metabolism in mammalian species and teleost fish is controlled by different metabolic pathways. These include differences in the function of several major hormones, especially insulin and GLP-1. The major physiological role of GLP-1 in mammals is to connect the consumption of nutrients with glucose metabolism. The glucose lowering effects of GLP-1 in the postprandial state of mammals are regulated predominantly through metabolic pathways that integrate different physiological processes. These are: (i) stimulation of insulin release from the pancreatic b-cell during hyperglycemia and (ii) inhibition of nutrient absorption in the gastrointestinal tract. These effects are mediated by a same type of a highly selective GLP-1 receptor, often referred to as the ‘‘pancreatic GLP-1 receptor.’’ In teleost fish GLP-1 increases glucose levels through the activation of glycogenolysis and gluconeogenesis from liver. Functional characterization of the recombinant GLP-1 receptor from zebrafish, which is the first example of a recombinant fish GLP-1 receptor, demonstrated that zebrafish GLP-1 receptor has a binding specificity towards a wider range of GLP-1 structures than the mammalian GLP-1 receptor. This property of the zebrafish GLP-1 receptor, and most likely other fish GLP-1 receptors, sets apart the structure of the zebrafish GLP-1 receptor from the structures of mammalian GLP-1 receptors. These differences in the binding specificity between the zebrafish and mammalian GLP-1 receptors might reflect in part the differences in the mechanism by which GLP-1 regulates glucose metabolism in mammals and teleost fish.