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The proglucagon gene encodes multiple structurally related peptides with overlapping actions promoting the absorption and assimilation of ingested energy. Notably, glucagon has been developed pharmaceutically to treat hypoglycemia, and glucagon-like peptide-1 (GLP-1) receptor agonists are used for the therapy of type 2 diabetes and obesity. Here I describe the discovery of glucagon-like peptide-2 (GLP-2), a 33 amino acid peptide cosecreted together with GLP-1 from gut endocrine cells. GLP-2 was found to exhibit robust intestinal growth-promoting activity, following serendipitous observations that proglucagon-producing tumors induced intestinal growth in mice. Key developments in the pharmaceutical development of GLP-2 included the cloning of the GLP-2 receptor, and the recognition of the importance of dipeptidyl peptidase-4 as a critical determinant of GLP-2 bioactivity. A therapeutic focus on short bowel syndrome, a serious medical disorder with compelling unmet medical need, enabled the pharmaceutical development of a simple GLP-2 analogue, teduglutide, suitable for once daily administration.

The Discovery of GLP-2 and Development of Teduglutide for Short Bowel Syndrome