title: Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats.
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.
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy. riccarda.granata@unito.it
authors.forename: Riccarda
authors.initials: R
authors.lastname: Granata
authors.forename: Fabio
authors.initials: F
authors.lastname: Settanni
authors.forename: Michel
authors.initials: M
authors.lastname: Julien
authors.forename: Rita
authors.initials: R
authors.lastname: Nano
authors.forename: Gabriele
authors.initials: G
authors.lastname: Togliatto
authors.forename: Antonella
authors.initials: A
authors.lastname: Trombetta
authors.forename: Davide
authors.initials: D
authors.lastname: Gallo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Piemonti
authors.forename: Maria Felice
authors.initials: MF
authors.lastname: Brizzi
authors.forename: Thierry
authors.initials: T
authors.lastname: Abribat
authors.forename: Aart-Jan
authors.initials: AJ
authors.lastname: van Der Lely
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D054439:Ghrelin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D057786:Peptidomimetics / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D013237:Stereoisomerism; D013311:Streptozocin; D013329:Structure-Activity Relationship
chemical_list: D054439:Ghrelin; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D057786:Peptidomimetics; D013311:Streptozocin