Oxyntomodulin: Actions and role in diabetes

•Oxyntomodulin is co-secreted with GLP-1 and glicentin from the intestinal L-cells.•Oxyntomodulin has glucagon-like bioactivity and also activates the GLP-1R.•Oxyntomodulin is as such a naturally occurring glucagon and GLP-1 receptor co-agonist. Oxyntomodulin is a product of the glucagon precursor, proglucagon, produced and released from the endocrine L-cells of the gut after enzymatic processing by the precursor prohormone convertase 1/3. It corresponds to the proglucagon sequence 33–69 and thus contains the entire glucagon sequence plus a C-terminal octapeptide, comprising in total 37 amino acids. As might have been expected, it has glucagon-like bioactivity, but also and more surprisingly also activates the receptor for GLP-1. This has given the molecule an interesting status as a glucagon-GLP-1 co-agonist, which is currently attracting considerable interest for its potential in the treatment of diabetes and obesity. Here, we provide an update on oxyntomodulin with a focus on its potential role in metabolic diseases.