Evolution of genes for incretin hormones and their receptors.

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are essential components in the regulation of blood glucose levels in mammals. These two incretins are produced by evolutionarily related genes and these hormones show similarity in sequence as both are glucagon-like sequences. Genes for these hormones have been identified in a number of diverse vertebrate species indicating that they originated prior to the earliest divergences of vertebrate species. However, analysis of functional and sequence data suggest that each of these hormones acquired incretin activity independently, and only since the divergence of tetrapods from fish. Not only are the hormones related, but so are their receptors. Like the hormones, the incretin action of the receptors is not a product of a shared common ancestral history, as the receptors for GLP-1 and GIP are not most closely related. Further study of the physiological functions of GLP-1 and GIP in additional vertebrates is required to better understand the origin of incretin action.