Emerging therapeutic potential for xenin and related peptides in obesity and diabetes

Xenin‐25 is a 25 amino acid peptide hormone co‐secreted from the same enteroendocrine K‐cell as the incretin peptide glucose‐dependent insulinotropic polypeptide (GIP). There is no known specific receptor for xenin‐25, but studies suggest that at least some biological actions may be mediated through interaction with the neurotensin receptor. Original investigation into the physiological significance of xenin‐25 focussed on effects related to gastrointestinal transit and satiety. However, xenin‐25 has been demonstrated in pancreatic islets and recently shown to possess actions in relation to the regulation of insulin and glucagon secretion, as well as promoting beta‐cell survival. Accordingly, the beneficial impact of xenin‐25, and related analogues, has been assessed in animal models of diabetes‐obesity. In addition, studies have demonstrated that metabolically active fragment peptides of xenin‐25, particularly xenin‐8, possess independent therapeutic promise for diabetes, as well as serving as bioactive components for the generation of multi‐acting hybrid peptides with antidiabetic potential. This review will focus on continuing developments with xenin compounds in relation to new therapeutic approaches for diabetes‐obesity.