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

Diabetes Metab Res Rev. 2018 Sep;34(6):e3006. doi: 10.1002/dmrr.3006. Epub 2018 Apr 26.

Abstract

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. 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 focuses on continuing developments with xenin compounds in relation to new therapeutic approaches for diabetes-obesity.

Keywords: diabetes; glucose-dependent insulinotropic polypeptide (GIP); insulin secretion; satiety; xenin-25.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Neurotensin / therapeutic use*
  • Obesity / drug therapy*
  • Peptide Fragments / therapeutic use
  • Peptides / therapeutic use
  • Therapies, Investigational / methods
  • Therapies, Investigational / trends*

Substances

  • Hypoglycemic Agents
  • Peptide Fragments
  • Peptides
  • xenin-8
  • xenin 25
  • Neurotensin