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 β-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.