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 journalArticle

33 Citations (Scopus)

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

Fingerprint

Experimental Diabetes Mellitus
Islets of Langerhans
Cell Survival
Ghrelin Receptor
des-n-octanoyl ghrelin
Amino Acid Substitution
Cyclization
Lipid Metabolism
Alanine
Serine
Oxidative Stress
Glucose

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats. / 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; Ghigo, Ezio.

In: Journal of Medicinal Chemistry, Vol. 55, No. 6, 22.03.2012, p. 2585-2596.

Research output: Contribution to journalArticle

Granata, R, Settanni, F, Julien, M, Nano, R, Togliatto, G, Trombetta, A, Gallo, D, Piemonti, L, Brizzi, MF, Abribat, T, Van Der Lely, AJ & Ghigo, E 2012, 'Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats', Journal of Medicinal Chemistry, vol. 55, no. 6, pp. 2585-2596. https://doi.org/10.1021/jm201223m
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 ; Ghigo, Ezio. / Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 6. pp. 2585-2596.
@article{cfbee9f5d69242e0a130c3fb6134fd51,
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.",
author = "Riccarda Granata and Fabio Settanni and Michel Julien and Rita Nano and Gabriele Togliatto and Antonella Trombetta and Davide Gallo and Lorenzo Piemonti and Brizzi, {Maria Felice} and Thierry Abribat and {Van Der Lely}, {Aart Jan} and Ezio Ghigo",
year = "2012",
month = "3",
day = "22",
doi = "10.1021/jm201223m",
language = "English",
volume = "55",
pages = "2585--2596",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "6",

}

TY - JOUR

T1 - Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats

AU - Granata, Riccarda

AU - Settanni, Fabio

AU - Julien, Michel

AU - Nano, Rita

AU - Togliatto, Gabriele

AU - Trombetta, Antonella

AU - Gallo, Davide

AU - Piemonti, Lorenzo

AU - Brizzi, Maria Felice

AU - Abribat, Thierry

AU - Van Der Lely, Aart Jan

AU - Ghigo, Ezio

PY - 2012/3/22

Y1 - 2012/3/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84858731418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858731418&partnerID=8YFLogxK

U2 - 10.1021/jm201223m

DO - 10.1021/jm201223m

M3 - Article

C2 - 22352743

AN - SCOPUS:84858731418

VL - 55

SP - 2585

EP - 2596

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 6

ER -