Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats

Riccarda Granata, Fabio Settanni, Michel Julien, Rita Nano, Gabriele Togliatto, Antonella Trombetta, Davide Gallo, Lorenzo Piemonti, Maria Felice Brizzi, Thierry Abribat, Aart Jan Van Der Lely, Ezio Ghigo

Research output: Contribution to journalArticlepeer-review

Abstract

Des-acyl ghrelin, although devoid of binding to ghrelin receptor (GRLN), exerts many biological effects, including regulation of glucose and lipid metabolism. Indeed, des-acyl ghrelin promotes pancreatic β-cell and human islet cell survival and prevents diabetes in streptozotocin (STZ) treated rats. We investigated whether des-acyl ghrelin fragments excluding serine 3, which is essential for binding to GRLN, would display similar actions. Among the different compounds tested, des-acyl ghrelin (6-13) and des-acyl ghrelin (6-13) with alanine substitutions or cyclization, but not with d-amino acid substitutions, showed the best survival effect, similar to des-acyl ghrelin. Des-acyl ghrelin (6-13) even prevented diabetes in STZ-treated rats and protected human circulating angiogenic cells from oxidative stress and senescence, similar to des-acyl ghrelin. These results suggest that not only full-length des-acyl ghrelin but also short des-acyl ghrelin fragments have clear beneficial effects on several tissues in vitro and in vivo.

Original languageEnglish
Pages (from-to)2585-2596
Number of pages12
JournalJournal of Medicinal Chemistry
Volume55
Issue number6
DOIs
Publication statusPublished - Mar 22 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats'. Together they form a unique fingerprint.

Cite this