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

Volumn 55, Issue 6, 2012, Pages 2585-2596

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

^a UNIVERSITY OF TURIN   (Italy)

^b UNIVERSITY OF TURIN   (Italy)

^c Alizé Pharma   (France)

^d SAN RAFFAELE HOSPITAL   (Italy)

^e ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; DEXTRO AMINO ACID; GHRELIN; SERINE; STREPTOZOCIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL SURVIVAL; CYCLIZATION; FEMALE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; OXIDATIVE STRESS; PANCREAS ISLET BETA CELL; RAT; SENESCENCE; STREPTOZOCIN DIABETES; SUBSTITUTION REACTION;

AMINO ACID SEQUENCE; ANIMALS; CELL AGING; CELL LINE; CELL SURVIVAL; DIABETES MELLITUS, EXPERIMENTAL; ENDOTHELIAL CELLS; GHRELIN; HUMANS; INSULIN-SECRETING CELLS; ISLETS OF LANGERHANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; OXIDATIVE STRESS; PEPTIDE FRAGMENTS; PEPTIDES, CYCLIC; PEPTIDOMIMETICS; RATS; RATS, SPRAGUE-DAWLEY; STEM CELLS; STEREOISOMERISM; STREPTOZOCIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84858731418     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201223m     Document Type: Article

References (43)

1. Kojima, M.; Hosoda, H.; Date, Y.; Nakazato, M.; Matsuo, H.; Kangawa, K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach Nature 1999, 402, 656-660 (Pubitemid 129516334)
2. Gnanapavan, S.; Kola, B.; Bustin, S. A.; Morris, D. G.; McGee, P.; Fairclough, P.; Bhattacharya, S.; Carpenter, R.; Grossman, A. B.; Korbonits, M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans J. Clin. Endocrinol. Metab. 2002, 87, 2988
3. van der Lely, A. J.; Tschop, M.; Heiman, M. L.; Ghigo, E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin Endocr. Rev. 2004, 25, 426-457 (Pubitemid 38780667)
4. Howard, A. D.; Feighner, S. D.; Cully, D. F.; Arena, J. P.; Liberator, P. A.; Rosenblum, C. I.; Hamelin, M.; Hreniuk, D. L.; Palyha, O. C.; Anderson, J.; Paress, P. S.; Diaz, C.; Chou, M.; Liu, K. K.; McKee, K. K.; Pong, S. S.; Chaung, L. Y.; Elbrecht, A.; Dashkevicz, M.; Heavens, R.; Rigby, M.; Sirinathsinghji, D. J.; Dean, D. C.; Melillo, D. G.; Patchett, A. A.; Nargund, R.; Griffin, P. R.; DeMartino, J. A.; Gupta, S. K.; Schaeffer, J. M.; Smith, R. G.; Van der Ploeg, L. H. A receptor in pituitary and hypothalamus that functions in growth hormone release Science 1996, 273, 974-977 (Pubitemid 26275178)
5. Sun, Y.; Wang, P.; Zheng, H.; Smith, R. G. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 4679-4684 (Pubitemid 38437470)
6. Davenport, A. P.; Bonner, T. I.; Foord, S. M.; Harmar, A. J.; Neubig, R. R.; Pin, J. P.; Spedding, M.; Kojima, M.; Kangawa, K. International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function Pharmacol. Rev. 2005, 57, 541-546 (Pubitemid 43036440)
7. Gutierrez, J. A.; Solenberg, P. J.; Perkins, D. R.; Willency, J. A.; Knierman, M. D.; Jin, Z.; Witcher, D. R.; Luo, S.; Onyia, J. E.; Hale, J. E. Ghrelin octanoylation mediated by an orphan lipid transferase Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 6320-6325 (Pubitemid 351758344)
8. Yang, J.; Brown, M. S.; Liang, G.; Grishin, N. V.; Goldstein, J. L. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone Cell 2008, 132, 387-396 (Pubitemid 351192001)
9. Granata, R.; Baragli, A.; Settanni, F.; Scarlatti, F.; Ghigo, E. Unraveling the role of the ghrelin gene peptides in the endocrine pancreas J. Mol. Endocrinol. 2010, 45, 107-118
10. Heppner, K. M.; Tong, J.; Kirchner, H.; Nass, R.; Tschop, M. H. The ghrelin O -acyltransferase-ghrelin system: a novel regulator of glucose metabolism Curr. Opin. Endocrinol., Diabetes Obes. 2011, 18, 50-55
11. Varela, L.; Vazquez, M. J.; Cordido, F.; Nogueiras, R.; Vidal-Puig, A.; Dieguez, C.; Lopez, M. Ghrelin and lipid metabolism: key partners in energy balance J. Mol. Endocrinol. 2011, 46, R43-R63
12. Delhanty, P. J.; van der Lely, A. J. Ghrelin and glucose homeostasis Peptides 2011, 32, 2309-2318
13. Dezaki, K.; Sone, H.; Koizumi, M.; Nakata, M.; Kakei, M.; Nagai, H.; Hosoda, H.; Kangawa, K.; Yada, T. Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance Diabetes 2006, 55, 3486-3493 (Pubitemid 44923609)
14. Sun, Y.; Asnicar, M.; Saha, P. K.; Chan, L.; Smith, R. G. Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice Cell Metab. 2006, 3, 379-386
15. Vestergaard, E. T.; Gormsen, L. C.; Jessen, N.; Lund, S.; Hansen, T. K.; Moller, N.; Jorgensen, J. O. Ghrelin infusion in humans induces acute insulin resistance and lipolysis independent of GH-signaling Diabetes 2008, 12, 3205
16. Barazzoni, R.; Zanetti, M.; Cattin, M. R.; Visintin, L.; Vinci, P.; Cattin, L.; Stebel, M.; Guarnieri, G. Ghrelin enhances in vivo skeletal muscle but not liver AKT signaling in rats Obesity 2007, 15, 2614-2623
17. Togliatto, G.; Trombetta, A.; Dentelli, P.; Baragli, A.; Rosso, A.; Granata, R.; Ghigo, D.; Pegoraro, L.; Ghigo, E.; Brizzi, M. F. Unacylated ghrelin rescues endothelial progenitor cell function in individuals with type 2 diabetes Diabetes 2010, 59, 1016-1025
18. Delhanty, P. J.; Sun, Y.; Visser, J. A.; van Kerkwijk, A.; Huisman, M.; van Ijcken, W. F.; Swagemakers, S.; Smith, R. G.; Themmen, A. P.; van der Lely, A. J. Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice PLoS One 2010, 5, e11749
19. Gauna, C.; Meyler, F. M.; Janssen, J. A.; Delhanty, P. J.; Abribat, T.; van Koetsveld, P.; Hofland, L. J.; Broglio, F.; Ghigo, E.; van der Lely, A. J. Administration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity J. Clin. Endocrinol. Metab. 2004, 89, 5035-5042 (Pubitemid 39391445)
20. Muccioli, G.; Pons, N.; Ghe, C.; Catapano, F.; Granata, R.; Ghigo, E. Ghrelin and des-acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a non-type 1a growth hormone secretagogue receptor Eur. J. Pharmacol. 2004, 498, 27-35 (Pubitemid 39208057)
21. Filigheddu, N.; Gnocchi, V. F.; Coscia, M.; Cappelli, M.; Porporato, P. E.; Taulli, R.; Traini, S.; Baldanzi, G.; Chianale, F.; Cutrupi, S.; Arnoletti, E.; Ghe, C.; Fubini, A.; Surico, N.; Sinigaglia, F.; Ponzetto, C.; Muccioli, G.; Crepaldi, T.; Graziani, A. Ghrelin and des-acyl ghrelin promote differentiation and fusion of C2C12 skeletal muscle cells Mol. Biol. Cell 2007, 18, 986-994 (Pubitemid 46399502)
22. Granata, R.; Settanni, F.; Biancone, L.; Trovato, L.; Nano, R.; Bertuzzi, F.; Destefanis, S.; Annunziata, M.; Martinetti, M.; Catapano, F.; Ghe, C.; Isgaard, J.; Papotti, M.; Ghigo, E.; Muccioli, G. Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3′,5′-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-kinase/Akt signaling Endocrinology 2007, 148, 512-529 (Pubitemid 46143157)
23. Mandrup-Poulsen, T. beta-Cell apoptosis: stimuli and signaling Diabetes 2001, 50 (Suppl. 1) S58-S63
24. Muoio, D. M.; Newgard, C. B. Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes Nat. Rev. Mol. Cell Biol. 2008, 9, 193-205 (Pubitemid 351301824)
25. Granata, R.; Volante, M.; Settanni, F.; Gauna, C.; Ghe, C.; Annunziata, M.; Deidda, B.; Gesmundo, I.; Abribat, T.; van der Lely, A. J.; Muccioli, G.; Ghigo, E.; Papotti, M. Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats J. Mol. Endocrinol. 2010, 45, 9-17
26. Kim, K. A.; Lee, M. S. Recent progress in research on beta-cell apoptosis by cytokines Front. Biosci. 2009, 14, 657-664
27. Drucker, D. J. The biology of incretin hormones Cell Metab. 2006, 3, 153-165
28. Le Marec, O.; Neveu, C.; Lefranc, B.; Dubessy, C.; Boutin, J. A.; Do-Rego, J. C.; Costentin, J.; Tonon, M. C.; Tena-Sempere, M.; Vaudry, H.; Leprince, J. Structure-activity relationships of a series of analogues of the RFamide-related peptide 26RFa J. Med. Chem. 2011, 54, 4806-4814
29. Hong, S. Y.; Oh, J. E.; Lee, K. H. Effect of d -amino acid substitution on the stability, the secondary structure, and the activity of membrane-active peptide Biochem. Pharmacol. 1999, 58, 1775-1780 (Pubitemid 29505418)
30. Hess, S.; Ovadia, O.; Shalev, D. E.; Senderovich, H.; Qadri, B.; Yehezkel, T.; Salitra, Y.; Sheynis, T.; Jelinek, R.; Gilon, C.; Hoffman, A. Effect of structural and conformation modifications, including backbone cyclization, of hydrophilic hexapeptides on their intestinal permeability and enzymatic stability J. Med. Chem. 2007, 50, 6201-6211
31. Craik, D. J. Chemistry. Seamless proteins tie up their loose ends Science 2006, 311, 1563-1564
32. Irako, T.; Akamizu, T.; Hosoda, H.; Iwakura, H.; Ariyasu, H.; Tojo, K.; Tajima, N.; Kangawa, K. Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats Diabetologia 2006, 49, 1264-1273
33. Tepper, O. M.; G., R.; Capla, J. M.; Kalka, C; Gagne, P. J.; Jacobowitz, G. R.; Levine, J. P.; Gurtner, G. C. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures Circulation 2002, 106, 2781-2786 (Pubitemid 35396976)
34. Hill, J. M.; Zalos, G.; Halcox, J. P.; Schenke, W. H.; Waclawiw, M. A.; Quyyumi, A. A.; Finkel, T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk N. Engl. J. Med. 2003, 348, 593-600 (Pubitemid 36204953)
35. Gao, L; M., G. Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling Cardiovasc. Res. 2009, 82, 9-20
36. 1H NMR structural analysis of human ghrelin and its six truncated analogs Biopolymers 2001, 59, 489-501 (Pubitemid 33150845)
37. Beevers, A. J.; Kukol, A. Conformational flexibility of the peptide hormone ghrelin in solution and lipid membrane bound: a molecular dynamics study J. Biomol. Struct. Dyn. 2006, 23, 357-364
38. Staes, E.; Absil, P. A.; Lins, L.; Brasseur, R.; Deleu, M.; Lecouturier, N.; Fievez, V.; Rieux, A.; Mingeot-Leclercq, M. P.; Raussens, V.; Preat, V. Acylated and unacylated ghrelin binding to membranes and to ghrelin receptor: towards a better understanding of the underlying mechanisms Biochim. Biophys. Acta 2010, 1798, 2102-2113
39. Granata, R.; Settanni, F.; Gallo, D.; Trovato, L.; Biancone, L.; Cantaluppi, V.; Nano, R.; Annunziata, M.; Campiglia, P.; Arnoletti, E.; Ghe, C.; Volante, M.; Papotti, M.; Muccioli, G.; Ghigo, E. Obestatin promotes survival of pancreatic beta-cells and human islets and induces expression of genes involved in the regulation of beta-cell mass and function Diabetes 2008, 57, 967-979
40. Bednarek, M. A.; Feighner, S. D.; Pong, S. S.; McKee, K. K.; Hreniuk, D. L.; Silva, M. V.; Warren, V. A.; Howard, A. D.; Van Der Ploeg, L. H.; Heck, J. V. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a J. Med. Chem. 2000, 43, 4370-4376 (Pubitemid 32046862)
41. Holst, B.; Brandt, E.; Bach, A.; Heding, A.; Schwartz, T. W. Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling Mol. Endocrinol. 2005, 19, 2400-2411 (Pubitemid 41252832)
42. Merrifield, R. B. Solid-phase peptide synthesis. 3. An improved synthesis of bradykinin Biochemistry 1964, 3, 1385-1390
43. Yoder, M. C.; Mead, L. E.; Prater, D.; Krier, T. R.; Mroueh, K. N.; Li, F.; Krasich, R.; Temm, C. J.; Prchal, J. T.; Ingram, D. A. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals Blood 2007, 109, 1801-1809 (Pubitemid 46348173)