Des-Acyl Ghrelin Fragments and Analogues Promote Survival of Pancreatic beta-Cells and Human Pancreatic Islets and Prevent Diabetes in Streptozotocin-Treated Rats

作者：Granata Riccarda^*; Settanni Fabio; Julien Michel; Nano Rita; Togliatto Gabriele; Trombetta Antonella; Gallo Davide; Piemonti Lorenzo; Brizzi Maria Felice; Abribat Thierry; van Der Lely Aart Jan; Ghigot Ezio

来源：Journal of Medicinal Chemistry, 2012, 55(6): 2585-2596.

DOI：10.1021/jm201223m

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 beta-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.

• 出版日期2012-3-22