Modulators of the ghrelin system as potential treatments for obesity and diabetes

Bibliography

• Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-60
   PubMed Web of Science ®Google Scholar
• Yang J, Brown MS, Liang G, et al. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 2008;132:387-96
   PubMed Web of Science ®Google Scholar
• Gutierrez JA, Solenberg PJ, Perkins DR, et al. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci USA 2008;105:6320-5
   PubMed Web of Science ®Google Scholar
• Broglio F, Gottero C, Prodam F, et al. Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab 2004;89:3062-5
   PubMed Web of Science ®Google Scholar
• Gauna C, Meyler FM, Janssen JA, et al. Administration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity. J Clin Endocrinol Metab 2004;89:5035-42
   PubMed Web of Science ®Google Scholar
• Hosoda H, Kojima M, Matsuo H, et al. Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 2000;279:909-13
   PubMed Web of Science ®Google Scholar
• Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996;273:974-7
   PubMed Web of Science ®Google Scholar
• Carpino PA. Recent developments in ghrelin receptor (GHS-R1a) agonists and antagonists. Expert Opinion on Therapeutic Patents 2002;12:1599-618
   Web of Science ®Google Scholar
• McKee KK, Palyha OC, Feighner SD, et al. Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors. Mol Endocrinol 1997;11:415-23
   PubMedGoogle Scholar
• Dezaki K, Kakei M, Yada T. Ghrelin uses Galphai2 and activates voltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet beta-cells: novel signal transduction of ghrelin. Diabetes 2007;56:2319-27
   PubMed Web of Science ®Google Scholar
• Holst B, Cygankiewicz A, Jensen TH, et al. High constitutive signaling of the ghrelin receptor - identification of a potent inverse agonist. Mol Endocrinol 2003;17:2201-10
   PubMed Web of Science ®Google Scholar
• Zigman JM, Jones JE, Lee CE, et al. Expression of ghrelin receptor mRNA in the rat and the mouse brain. J Comp Neurol 2006;494:528-48
   PubMed Web of Science ®Google Scholar
• Baldanzi G, Filigheddu N, Cutrupi S, et al. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 2002;159:1029-37
   PubMed Web of Science ®Google Scholar
• Popovic V, Miljic D, Micic D, et al. Ghrelin main action on the regulation of growth hormone release is exerted at hypothalamic level. J Clin Endocrinol Metab 2003;88:3450-3
   PubMed Web of Science ®Google Scholar
• Okimura Y, Ukai K, Hosoda H, et al. The role of circulating ghrelin in growth hormone (GH) secretion in freely moving male rats. Life Sci 2003;72:2517-24
   PubMed Web of Science ®Google Scholar
• Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000;407:908-13
   PubMed Web of Science ®Google Scholar
• Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001;409:194-8
   PubMed Web of Science ®Google Scholar
• Wren AM, Small CJ, Ward HL, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000;141:4325-8
   PubMed Web of Science ®Google Scholar
• Dezaki K, Sone H, Yada T. Ghrelin is a physiological regulator of insulin release in pancreatic islets and glucose homeostasis. Pharmacol Ther 2008;118:239-49
   PubMed Web of Science ®Google Scholar
• Sun Y, Asnicar M, Smith RG. Central and peripheral roles of ghrelin on glucose homeostasis. Neuroendocrinology 2007;86:215-28
   PubMed Web of Science ®Google Scholar
• Wiedmer P, Nogueiras R, Broglio F, et al. Ghrelin, obesity and diabetes. Nat Clin Pract Endocrinol Metab 2007;3:705-12
   PubMedGoogle Scholar
• Pusztai P, Sarman B, Ruzicska E, et al. Ghrelin: a new peptide regulating the neurohormonal system, energy homeostasis and glucose metabolism. Diabetes Metab Res Rev 2008;24:343-52
   PubMed Web of Science ®Google Scholar
• Cummings DE, Purnell JQ, Frayo RS, et al. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001;50:1714-9
   PubMed Web of Science ®Google Scholar
• Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002;346:1623-30
   PubMed Web of Science ®Google Scholar
• Asakawa A, Inui A, Kaga T, et al. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003;52:947-52
   PubMed Web of Science ®Google Scholar
• Tschop M, Weyer C, Tataranni PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001;50:707-9
   PubMed Web of Science ®Google Scholar
• Shuto Y, Shibasaki T, Otagiri A, et al. Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity. J Clin Invest 2002;109:1429-36
   PubMed Web of Science ®Google Scholar
• Zigman JM, Nakano Y, Coppari R, et al. Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest 2005;115:3564-72
   PubMed Web of Science ®Google Scholar
• Wortley KE, Anderson KD, Garcia K, et al. Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci USA 2004;101:8227-32
   PubMed Web of Science ®Google Scholar
• Wortley KE, del Rincon JP, Murray JD, et al. Absence of ghrelin protects against early-onset obesity. J Clin Invest 2005;115:3573-8
   PubMed Web of Science ®Google Scholar
• Shintani M, Ogawa Y, Ebihara K, et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 2001;50:227-32
   PubMed Web of Science ®Google Scholar
• Date Y, Nakazato M, Hashiguchi S, et al. Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. Diabetes 2002;51:124-9
   PubMed Web of Science ®Google Scholar
• Gnanapavan S, Kola B, Bustin SA, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002;87:2988
   PubMed Web of Science ®Google Scholar
• Wierup N, Svensson H, Mulder H, et al. The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept 2002;107:63-9
   PubMed Web of Science ®Google Scholar
• Dezaki K, Hosoda H, Kakei M, et al. Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in beta-cells: implication in the glycemic control in rodents. Diabetes 2004;53:3142-51
   PubMed Web of Science ®Google Scholar
• Broglio F, Arvat E, Benso A, et al. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 2001;86:5083-6
   PubMed Web of Science ®Google Scholar
• Egido EM, Rodriguez-Gallardo J, Silvestre RA, et al. Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. Eur J Endocrinol 2002;146:241-4
   PubMed Web of Science ®Google Scholar
• Sun Y, Asnicar M, Saha PK, et al. Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice. Cell Metab 2006;3:379-86
   PubMed Web of Science ®Google Scholar
• Longo KA, Charoenthongtrakul S, Giuliana DJ, et al. Improved insulin sensitivity and metabolic flexibility in ghrelin receptor knockout mice. Regul Pept 2008
   Google Scholar
• Lee HM, Wang G, Englander EW, et al. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 2002;143:185-90
   PubMed Web of Science ®Google Scholar
• Salehi A, Dornonville de la Cour C, Hakanson R, et al. Effects of ghrelin on insulin and glucagon secretion: a study of isolated pancreatic islets and intact mice. Regul Pept 2004;118:143-50
   PubMedGoogle Scholar
• Veeraragavan K, Sethumadhavan K, Bowers CY. Growth hormone-releasing peptide (GHRP) binding to porcine anterior pituitary and hypothalamic membranes. Life Sci 1992;50:1149-55
   PubMed Web of Science ®Google Scholar
• Zentaris A-G., Germany. Ghrelin antagonist peptides. WO2002008250; 2002
   Google Scholar
• Ardana Bioscience Limited, UK. Cortistatin analogs selective binding to growth hormone secretagogue receptors and uses in treatment of tumors, acromegaly and reduction of the appetite. WO2003004518; 2003
   Google Scholar
• Deghenghi R, Broglio F, Papotti M, et al. Targeting the ghrelin receptor: orally active GHS and cortistatin analogs. Endocrine 2003;22:13-8
   PubMed Web of Science ®Google Scholar
• Novo Nordisk A/S, Den. Use of ghrelin antagonists for therapy of CNS diseases. WO2005112903; 2005
   Google Scholar
• The Administrators of the Tulane Educational Fund, USA. Ghrelin/growth hormone releasing peptide/growth hormone secretagogue receptor antagonists and uses thereof. WO2007127457; 2007
   Google Scholar
• Societe de Conseils de Recherches et d'Applications Scientifiques S.A.S., Fr. Preparation of therapeutic analogs of ghrelin active at the GHS receptor. WO2007038678; 2007
   Google Scholar
• Societe de Conseils de Recherches et d'Applications Scientifiques S.a.S., Fr. Analogs of ghrelin substituted at the N-terminal for improved plasma stability and modulation of receptor activity. WO2008039415; 2008
   Google Scholar
• Cheng K, Chan WW, Butler B, et al. Stimulation of growth hormone release from rat primary pituitary cells by L-692,429, a novel non-peptidyl GH secretagogue. Endocrinology 1993;132:2729-31
   PubMed Web of Science ®Google Scholar
• 7TM Pharma A/S, Den. Ghrelin receptor inverse agonists for regulation of feeding behaviors. WO2004056869; 2004
   Google Scholar
• Liu B, Liu G, Xin Z, et al. Novel isoxazole carboxamides as growth hormone secretagogue receptor (GHS-R) antagonists. Bioorg Med Chem Lett 2004;14:5223-6
   PubMed Web of Science ®Google Scholar
• Zhao H, Liu G. Growth hormone secretagogue receptor antagonists as anti-obesity therapies? Still an open question. Curr Opin Drug Discov Devel 2006;9:509-15
   PubMedGoogle Scholar
• Zhao H, Xin Z, Liu G, et al. Discovery of tetralin carboxamide growth hormone secretagogue receptor antagonists via scaffold manipulation. J Med Chem 2004;47:6655-7
   PubMed Web of Science ®Google Scholar
• Abbott Laboratories, USA. Preparation of tetralin derivatives as ghrelin receptor modulators. US7115767; 2005
   Google Scholar
• Abbott Laboratories. Preparation of diaminopyrimidines as growth hormone secretagogue receptor (GHS-R) antagonists. US 2005171131; 2005
   Google Scholar
• Abbott Laboratories. A preparation of pyrimidine derivatives, useful as ghrelin receptor modulators. US 2005070712; 2005
   Google Scholar
• Serby Michael D, Zhao H, Szczepankiewicz Bruce G, et al. 2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor antagonists. J Med Chem 2006;49:2568-78
   PubMed Web of Science ®Google Scholar
• Xin Z, Serby Michael D, Zhao H, et al. Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists. J Med Chem 2006;49:4459-69
   PubMed Web of Science ®Google Scholar
• Biovitrum AB, Swed. Preparation of spiro(b-carbolinepyrrolidines) and related compounds as growth hormone secretagogue receptor (GHSR) antagonists. WO2005048916; 2005
   Google Scholar
• Amgen Inc., USA. Preparation of benzo-fused heterocycles for treatment of obesity and eating disorders. WO2006020959; 2006
   Google Scholar
• Elixir Pharmaceuticals, Inc., USA. Preparation of sulfonamide compounds as GHS-R modulators. WO2006135860; 2006
   Google Scholar
• Bayer Pharmaceuticals Corporation, USA. Preparation of quinazolinone derivatives useful for the regulation of glucose homeostasis and food intake. WO2006012577; 2006
   Google Scholar
• Esler WP, Rudolph J, Claus TH, et al. Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss. Endocrinology 2007;148:5175-85
   PubMed Web of Science ®Google Scholar
• Rudolph J, Esler WP, O'Connor S, et al. Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. J Med Chem 2007;50:5202-16
   PubMed Web of Science ®Google Scholar
• Acadia Pharmaceuticals Inc., USA. Bicyclic nitrogen compounds as modulators of ghrelin receptor and their preparation, pharmaceutical compositions and use in the treatment of diseases. WO2007079239; 2007
   Google Scholar
• Zentaris GmbH., Germany; Le Centre Mational de la Recherche Scientifique; University of Montpeller I; University of Montpeller II. Triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors, their preparation, pharmaceutical compositions, and use in therapy. WO2007020013; 2007
   Google Scholar
• Dainippon Sumitomo Pharma Co., Ltd., Japan. Preparation of oxindole derivatives as feeding control agents. WO2007032371; 2007
   Google Scholar
• Merck & Co., Inc., USA. Preparation of substituted pyrazoles as ghrelin receptor antagonists. WO2008008286; 2008
   Google Scholar
• Eli Lilly and Company, USA. Anti-human ghrelin antibodies and conjugates for diagnosis and therapy of obesity and related disorders. WO2005026211; 2005
   Google Scholar
• Eli Lilly and Company, USA. Anti-ghrelin antibodies. WO2006019577; 2006
   Google Scholar
• Eli Lilly and Company, USA. Humanized anti-ghrelin antibodies. WO2007101021; 2007
   Google Scholar
• The Scripps Research Institute, USA. Vaccine immunoconjugates comprising ghrelin polypeptides for control of obesity. WO2008016976; 2008
   Google Scholar
• Zorrilla EP, Iwasaki S, Moss JA, et al. Vaccination against weight gain. Proc Natl Acad Sci USA 2006;103:13226-31
   PubMed Web of Science ®Google Scholar
• Cytos Biotechnology Ag, Switz. Compositions and methods for producing ghrelin-carrier conjugates and uses as vaccines for antiobesity therapy. WO2004009124; 2004
   Google Scholar
• Cytos Biotechnology AG., Switz. Modified ghrelin peptide-VLP (virus-like particle) carrier conjugates, and immunogenic uses for the treatment of obesity. WO2005068639; 2005
   Google Scholar
• Cytos Biotechnology press release. Available from: http://www.cytos.com/?id=939
   Google Scholar
• Boston Biomedical Research Institute, USA. Ghrelin transition state analog, antibodies and enzymes specifically bind and/or cleave octanoylated native ghrelin for suppressing appetite/hunger and treating obesity and Prader-Willi syndrome. WO2007092023; 2007
   Google Scholar
• Noxxon Pharma A-G., Germany. Use of RNA-spiegelmers binding to n-octanoyl ghrelin for diagnosis and treatment of metabolic and cardiovascular diseases and cancer. WO2005049828; 2005
   Google Scholar
• Noxxon Pharma A.-G., Germany; Supramol Parenteral Colloid G.m.b.H. Method for producing conjugates of polysaccharides and polynucleotides for use as drug-delivery systems. WO2005074993; 2005
   Google Scholar
• Noxxon Pharma A.-G., Germany. Design of ribonucleic acid aptamers binding to n-octanoyl-ghrelin. WO2006108599; 2006
   Google Scholar
• Shearman LP, Wang SP, Helmling S, et al. Ghrelin neutralization by a ribonucleic acid-SPM ameliorates obesity in diet-induced obese mice. Endocrinology 2006;147:1517-26
   PubMed Web of Science ®Google Scholar
• Amylin Pharmaceuticals, Inc., USA. Methods for treating or ameliorating ghrelin-associated diseases and disorders. WO2005021026; 2005
   Google Scholar
• Field BC, Wren AM, Cooke D, et al. Gut hormones as potential new targets for appetite regulation and the treatment of obesity. Drugs 2008;68:147-63
   PubMed Web of Science ®Google Scholar
• Holst B, Schwartz TW. Constitutive ghrelin receptor activity as a signaling set-point in appetite regulation. Trends Pharmacol Sci 2004;25:113-7
   PubMed Web of Science ®Google Scholar
• Pfluger PT, Kirchner H, Gunnel S, et al. Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure. Am J Physiol Gastrointest Liver Physiol 2008;294:G610-8
   PubMed Web of Science ®Google Scholar