Glucagon-like peptide-1 (GLP-1) and the control of glucose metabolism in mammals and teleost fish

Glucose metabolism in mammalian species and teleost fish is controlled by d ifferent metabolic pathways. These include differences in the function of s everal major hormones, especially insulin and GLP-1, The major physiologica l 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 postprandi al state of mammals are regulated predominantly through metabolic pathways that integrate different physiological processes. These are: (i) stimulatio n of insulin release from the pancreatic beta-cell during hyperglycemia and (ii) inhibition of nutrient absorption in the gastrointestinal tract. Thes e 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 glu coneogenesis from liver. Functional characterization of the recombinant GLP -1 receptor from zebrafish, which is the first example of a recombinant fis h GLP-1 receptor, demonstrated that zebrafish GLP-1 receptor has a binding specificity towards a wider range of GLP-1 structures than the mammalian GL P-1 receptor. This property of the zebrafish GLP-1 receptor, and most likel y other fish GLP-1 receptors, sets apart the structure of the zebrafish GLP -1 receptor from the structures of mammalian GLP-1 receptors, These differe nces In the binding specificity between the zebrafish and mammalian GLP-1 r eceptors might reflect in part the differences in the mechanism by which GL P-1 regulates glucose metabolism in mammals and teleost fish.