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2015, Number 3

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Rev Med MD 2015; 6.7 (3)

The effects of ghrelin and obestatine over health and sickness

Llamas-Covarrubias IM, Ruiz-Solorio LS, Llamas-Covarrubias MA, Rivera-León EA, Sánchez-Enríquez S

Language: Spanish
References: 104
Page: 196-208
PDF size: 915.94 Kb.


ABSTRACT

Ghrelin and Obestatin are recently discovered hormones with important regulatory functions over appetite. Ghrelin is known as the first peripheral orexigenic hormone with central actions. One of its most important actions is to induce appetite, accelerate gastric emptying and it is mainly secreted before meals. On the other hand, obestatin has opposite actions to ghrelin over appetite regulation, glucose regulation and pancreatic beta cell survival.
Functions attributed to these hormones relate them to chronic pathological states, such as obesity and type 2 diabetes mellitus. They also play a role in other illnesses such as anorexia, kidney failure, heart disorders, etc. Genetic studies of these hormones show polymorphic variants that are related to weight increase and glucose intolerance susceptibility. Possible therapeutic uses of these hormones have been suggested.


REFERENCES

  1. Scerif M, Goldstone AP, Korbonits M. Ghrelin in obesity and endocrine diseases. Mol Cell Endocrinol. 2011 Jun 20;340(1):15-25.

  2. Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, et al. Obestatin peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science. 2005 Nov 11;310(5750):996-9.

  3. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormonereleasing acylated peptide from stomach. Nature. 1999 Dec 9;402(6762):656-60.

  4. Wajnrajch MP. Genetic disorders of human growth. J Pediatr Endocrinol Metab. 2002 May; 15 Suppl 2:701-14.

  5. Seim I, Collet C, Herington AC, Chopin LK. Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts. BMC Genomics. 2007 Aug 30;8:298.

  6. Seim I, Amorim L, Walpole C, Carter S, Chopi LK, Herington AC. Ghrelin gene-related peptides: multifunctional endocrine/autocrine modulators in health and disease. Clin Exp Pharmacol Physiol. 2010 Jan;37(1):125-31.

  7. Seim I, Herington AC, Chopin LK. New insights into the molecular complexity of the ghrelin gene locus. Cyto kine Growth Factor Rev. 2009 Aug;20(4):297-304.

  8. Hosoda H, Kojima M, Mizushima T, Shimizu S, Kangawa K. Stuctural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing. J Biol Chem. 2003 Jan 3;278(1):64-70.

  9. Kanamoto N, Akamizu T, Tagami T, Hataya Y, Moriyama K, Takaya K, et al. Genomic structure and characterization of the 5'-flanking región of the human ghrelin gene. Endocrinology. 2004 Sep;145(9):4144-53.

  10. Hughes TA. Regulation of gene expression by alternative untranslated regions. Tends Genet. 2006 Mar;22(3):119-22.

  11. Seim I, Carter SL, Herington AC, Chopin LK. Complex organisation and structure of the ghrelin antisense strand gene GHRLOS, a candidate noncoding RNA gene. BMC Mol Biol.2008 Oct 28;9:95.

  12. Futagami S, Shimpuku M, Kawagoe T, Izumi N, Ohishi N, Yamawaki H. The preproghrelin 3056 TT genotype is associated with the feeling of hunger and low acylated ghrelin levels in Japanese patients with Helicobacter pylori.negative functional dispepsia. Intern Med. 2013;52(11):1155- 63.

  13. 13.Ukkola O, Ravussin E, Jacobson P, Pérusse L, Rankinen T, Tscöp M, et al. Role of ghrelin polymorphisms in obesity base don three different studies. Obes Res. 2002 Aug;10(8):782-91.

  14. Liu B, Garcia EA, Korbonits M. Genetic studies on the ghrelin, growth hormone secretagogue receptor (GHSR) and ghrelin O-acyl transferase (GOAT) genes. Peptides.2011 Nov;32(11):2191-207.

  15. 15.Yaneva M, Kippenberger S, Wang N, Su Q, McGarvey M, Nazarian A. PU.1 and a TTTAAA element in the myeloid defensin-1 promoter create an operational TATA box that can impose cell specificity onto TFIID function. J Immunol. 2006 Jun 1;176(11):6906-17.

  16. 16.Yang Y, Li W, Zhao J, Zhang H, Song X, Xiao B, et al. Association between ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients. Behav Brain Funct.2012 Feb 28;8:11.

  17. Mager U, Kolehmainen M, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, et al. Association between ghrelin gene variations and blood pressure in subjects with impaired glucose tolerance. Am J Hypertens. 2006 Sep;19(9):920-6.

  18. 18.Campa D, Pardini B, Naccarati A, Vodickova L, Novotny J, Steinke V, et al. Polymorphisms of genes coding for ghrelin and its receptor in relation to colorectal cancer risk: a two-step gene-wide casecontrol study. BMC Gastroenterol. 2010 Sep 28;10:112.

  19. 19.Ber thold HK, Giannakidou E, Krone W, Mantzoros CS, Gouni-Berthold I. The Leu72Met polymorphism of the ghrelin gene is associated with a decreased risk for type 2 diabetes. Clin Chim Acta. 2009 Jan;399(1-2):112-6.

  20. Berthold HK, Giannakidou E, Krone W, Trégouët DA, Gouni-Berthold I. Influence of ghrelin gene polymorphismson hypertension and atherosclerotic disease. Hypertens Res. 2010 Feb;33(2):155-60.

  21. 21.Ukkola O, Ravussin E, Jacobson P, Snyder EE, Chagnon M, Sjöström L, Bouchard C. Mutations in the preproghrelin/ghrelin gene associated with obesity in humans. J Clin Endocrinol Metab. 2001 Aug;86(8):3996-9.

  22. Pöykkö SM1, Kellokoski E, Hörkkö S, Kauma H, Kesäniemi YA, Ukkola O. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes.2003 Oct;52(10):2546-53

  23. Krzyzanowska-Swiniarska B, Kempa A, Robaczyk M. Preproghrelin gene, ghrelin receptor and metabolic síndrome. Przegl Lek. 2005;62(4):230-3.

  24. 24 .Wang K, Wang L, Zhao Y, Shi Y, Wang L, Chen ZJ. No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene and polystic ovary síndrome. Hum Reprod. 2009 Feb;24(2):485- 90.

  25. 25.Zavarella S, Petrone A, Zampetti S, Gueorgiev M, Spoletini M, Mein CA, et al. A new variation in the promoter región, the -604C>T, and the Leu72Met polymorphism of the ghrelin gene are associated with protection to insulin resistance. Int J Obes (Lond). 2008 Apr;32(4):663-8.

  26. 26.Miraglia del Giudice E, Santoro N, Cirillo G, Raimondo P, Grandone A, D'Aniello A. Molecular screening of the ghrelin gene in Italiano bese children: the Leu72Met variant is associated with an earlier onset of obesity. Int J Obes Relat Metab Disord. 2004 Mar;28(3):447-50.

  27. 27.Takezawa J, Yamada K, Miyachi M, Morita A, Aiba N, Sasaki S, et al. Preproghrelin gene polymorphisms in obese Japanese women. Minor homozygotes are light eaters, do not prefer protein or fat, and apparently have a por appetite. Appetite. 2013 Apr;63:105-11.

  28. 28.Kilpeläinen TO, Lakka TA, Laaksonen DE, Mager U, Salopuro T, Kubaszek A, et al. et al. Finnish Diabetes Prevention Study Group. Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study. Metabolism. 2008 Mar;57(3):428- 36.

  29. 29.Kuzuya M, Ando F, Iguchi A, Shimokata H. Preproghrelin Leu72Met variant contributes to overweight in middle-aged men of a Japanese large cohort. Int J Obes (Lond). 2006 Nov;30(11):1609- 14.

  30. 30.Hassouna R, Zizzari P, Viltart O, Yang SK, Gardette R, Videau C, et al. A natural variant of obestatin, Q90L, inhibits ghrelin's action on food intaje and GH secretion and targets NPY and GHRHneuronsinmice. PLo SO ne. 2012;7(12):e51135.

  31. 31.Dardennes RM, Zizzari P, Tolle V, Foulon C, Kipman A, Romo L, et al. Family trios analysis of common olymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass index, severity and ageofonset. Psychoneuroendocrinology. 2007 Feb;32(2):106-13.

  32. 2.Gueorguiev M, Lecoeur C, Meyre D, Benzinou M, Mein CA, Hinney A, et al. Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity. Obesity (Silver Spring). 2009 Apr;17(4):745-54.

  33. Bing C, Ambye L, Fenger M, Jorgensen T, Borch- Johnsen K, Madsbad S, et al. Large-scale studies of the Leu72Met polymorphisms of the ghrelin gene on relation to the metabolic síndrome and associated quantitative traits. Dianet Med. 2005 Sep;22(9):1157-60.

  34. Tomasetto C, Karam SM, Ribieras S, Masson R, Lefèbvre O, Staub A, et al. Identification and characterization of a novel gastric peptide hormone: themotilin-related peptide. Gastroenterology. 2000 Aug;119(2):395-405.

  35. Gutierrez JA, Solenberg PJ, Perkins DR, Willency JA, Knierman MD, Jin Z, et al. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci USA. 2008 Apr 29;105(17):6320-5.

  36. 36.Yang J, Zhao TJ, Golstein JL, Brown MS. Inhibition of grelin O-acyltransferase (GOAT) by octanoylated pentapeptides. Proc Natl Acad Sci USA. 2008 Aug 5;105(31):10750-5.

  37. 37.Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology. 2000 Nov;141(11):4255-61.

  38. Patterson M, Murphy KG, le Roux CW, Chatei MA, Bloom SR. Characterization of ghrelin-like immunoreactivity in human plasma. J Clin Endocrinol Metab. 2005 Apr;90(4):2205-11.

  39. Akamizu T, Shinomiya T, Irako T, Fukunaga M, Nakai Y, Kangawa K. Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy subjects usin a new direct ELISA assay. J Clin Endocrinol Metab. 2005 Jan;90(1):6-9.

  40. Delporte C. Structure and physiological actions of ghrelin. Scientidica (Cairo). 2013;2013:518909.

  41. 41.Leite-Moreira AF, Soares JB. Physiological, pathological and potential therapeutic roles of ghrelin. Drug Discov Today. 2007 Apr;12(7-8):276- 88.

  42. 42.Yoh J, Nishi Y, Hosod H, Tajiri Y, Yamada K, Yanase T, et al. Plasma lebels of n-decanoyl ghrelin, another acyl- and active-form of ghrelin, in human subjects and the effect of glucose- or mealingestion on its dynamics. Regul Pept. 2011 Feb 25;167(1):140-8.

  43. 43.Rindi G, Leiter AB, Kopin AS, Bordi C, Solcia E. The “normal” endocrine cell of the gut: changing concepts and new evidences. Ann N Y Acad Sci. 2004 Apr;1014:1-12.

  44. 44.Stengel A, Taché Y. Yin and Yang – the Gastric X/A-like Cell as Possible Dual Regulator of Food In take. JNeurogastroenterol Motil. 2012 Apr;18(2):138-49.

  45. 45.Bowers CY, Momany F, Reynolds GA, Chang D, Hong A, Chang K. Structure-activity relationships of a synthetic pentapeptide that specifically releases growth hormone in vitro. Endocrinology. 1980 Mar;106(3):663-7.

  46. 46.Tschöp M, Smiley DL, Heiman ML. Ghrelin índices adiposity in rodents. Nature. 2000 Oct 19;407(6806):908-13.

  47. Higgins SC, Gueorgiev M, Korbonits M. Ghrelin, the peripheral hunger hormone. Ann Med. 2007;39(2):116-36.

  48. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005 Apr;85(2):495-522.

  49. Cummings DE. Ghrelin and the short-and longterm regulation of appetite and body weight. Physiol Behav. 2006 Aug 30;89(1):71-84.

  50. 50.Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001 Jan 11;409(6817):194-8.

  51. 51.Wortley KE, del Rincon JP, Murray JD, Garcia K, lidia K, Thorner MO, et al. Absence of ghrelin protects against early-onset obesity. J Clin Invest. 2005 Dec; 115(12):3573-8.

  52. 52.Sun Y, Butte NF, Garcia JM, Smith RG. Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance. Endocrinology. 2008 Feb;149(2):843- 50.

  53. H eppner KM , Tong J. Mechanismsin endoctinology: regulation of glucose metabolism by the ghrelin system: multiple players and multiple actions. Eur J Endocrinol. 2014 Jul;171(1):R21-32.

  54. 54.Date Y, Nakazato M, Murakami N, Kojima M, Kangawa K, Matsukura S. Ghrelin acts in the central nervous system to stimulate gastric acid secretion. Biochem Biophys Res Commun. 2001 Jan 26;280(3):904-7.

  55. 55.Pöykkö SM, Kellokoski E, Hörkkö S, Kauma H, Kesäniemi YA, Ukkola O. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes. 2003 Oct;52(10):2546-53.

  56. 56 .Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiatio ninhumans. Diabetes. 2001 Aug;50(8):1714-9.

  57. 57.Schmidt PT, Degerblad M, Lindström E, Sundqvist M, Näslund E, Gillberg PG, et al. Circulating ghrelin levels after food intake during different phases of the migrating motor complex in man. Eur J Clin Invest. 2006 Jul;36(7):503-8.

  58. 58.Holst B, Holliday ND, Bach A, Elling CE, Cox HM, Schwartz TW. Common structural basis for constitutive activity of the ghrelin receptor family. J Biol Chem. 2004 Dec 17;279(51):53806-17.

  59. 59.Petersenn S, Rasch AC, Penshom M, Beil FU, Schulte HM. Genomicstructure and transcriptional regulation of the human growth hormone secretagogue receptor. Endocrinology. 2001 Jun;142(6):2649-59.

  60. 60 .Ghigo E, Broglio F, Arvat E, Maccario M, Papotti M, Muccioli G. Ghrelin: more tan a natural GH secretagogue and/ora n orexigenic factor. Clin Endocrinol (Oxf). 2005 Jan;62(1):1-17.

  61. Sibila V, Muccioli G, Deghenghi R, Pagani F, De Luca V, Rapetti D, et al. Evidence for a role of the GHS-R1a receptors in ghrelin inhibition of gastric acid secretion in the rat. J Neuroendocrinol. 2006 Feb;18(2):122-8.

  62. 62.van der Lely AJ, Tschöp M, Heiman ML, Ghigo E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev, 2004 Jun;25(3):426-57.

  63. 63.Seoane LM, Al-Massadi O, Lage M, Dieguez C, Casanueva FF. Ghrelin:from a GH-secretagogue to the regulation of food intake, sleep and anxiety. Pediatr Endocrinol Rev. 2004 Aug;1 Suppl 3:432-7.

  64. 64.Egecioglu E, Stenström B, Pinnock SB, Tung LY, Dornonville de la Cour C, Lindqvist A, et al. Hypothalamic gene expression following ghrelin therapy to gastrectomized rodents. Regul Pept. 2008 Feb 7;146(1-3):176-82.

  65. 65.Chen CY, Asakawa A, Fujimiya M, Lee SD, Inui A. Ghrelin gene products and the regulation of food intake and gut motility. Pharmacol Rev. 2009 Dec;61(4):430-81

  66. 66.Kola B, Boscaro M, Rutter GA, Grossman AB, Korbonits M. Expanding role of AMPK in endocrinology. Trends Endocrinol Metab. 2006 Jul;17(5):205-15.

  67. 67.Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 2004 Apr1;428(6982):569-74.

  68. 68.Lim CT, Kola B, Korbonits M. AMPK as a mediator of hormonal signalling. J Mol Endocrinol. 2010 Feb;44(2):87-97.

  69. 69.López M, Lage R, Saha AK, Pérez-Tilve D, Vázquez MJ, Varela L, et al. Hypothalamic fatty acid metabolism mediates the orexigenic action od ghrelin. Cell Metab. 2008 May;7(5):389-99.

  70. Kola B, Hubina E, Tucci SA, Kirkham TC, Garcia EA, Mitchell SE, et al. Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J Biol Chem. 2005 Jul 1;280(26):25196-201.

  71. Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF, Muehlbauer MJ, et al. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab. 2008 May;7(5):377-88.

  72. 72.Cummings DE, Frayo RS, Marmonier C, Aubert R, Chapelot D. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time-and food-related cues. Am J Physiol Endocrinol Metab.2004 Aug;287(2):E297-304

  73. 73.Callahan HS, Cummings DE, Pepe Ms, Breen PA, Matthys CC, Weigle DS. Postprandial suppression of plasma ghrelin leve lis proportional to ingested caloric load but does not predict intermeal interval in humans. J Clin Endocrinol Metab. 2004 Mar;89(3):1319-24

  74. 74.Briggs DI, Enriori PJ, Lemus MB, Cowley MA, Andrews ZB. Diet-induced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons. Endocrinology. 2010 Oct;151(10):4745-55.

  75. 75.Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001 Apr;50(4):707-9.

  76. 76.Goldstone AP, Thomas EL, Brynes AE, Castroman G, Edwards R, Ghatei MA, et al. Elevated fasting plasma ghrelin in prader-willi síndrome adults is not solely explained by their reduced visceral adiposity and insulin resistance. J Clin Endocrinol Metab. 2004 Apr;89(4):1718-26.

  77. 77.Zhu JF, Liang L, Zou CC, Fu JF. Plasma ghrelin levels and polymorphisms of ghrelin gene in Chinese obese children and adolescents. Ir J Med Sci. 2010 Sep;179(3):345-9.

  78. 78.Shearman LP, Wang SP, Helmling S, Stribling DS, Mazur P, Ge L, et al. Ghrelin neutralization by a ribonucleica cid-SPM ameliorates obesity in dietin ducedobesemice. Endocrinology. 2006 Mar;147(3):1517-26.

  79. 79.Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone reléase and appetite is mediates through the g rowth hormone secretagogue receptor. Proc Natl Acad Sci USA. 2004 Mar 30;101(13):4679-84.

  80. 80.Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, et al. Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest. 2005 Dec; 115(12):3564-72.

  81. Asakawa A, Inui A, Kaga T, Katsuura G, Fujimiya M, Fujino MA, et al. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut. 2003 Jul;52(7):947-52.

  82. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002 Jan;87(1):240-4.

  83. 83.Tack J, Depoortere I, Bisschops R, et al. Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Aliment Pharmacol Ther. 2005 Nov 1;22(9):847-53.

  84. Milijic D, Pekic S, Djurovic M, et al. Ghrelin has partial or no effect on appetite, growth hormone, prolactin, and cortisol reléase in patients with anorexia nervosa. J Clin Endocrinol Metab. 2006 Apr;91(4):1491-5.

  85. 85.Deboer MD, Zhu X, Lebasseur PR, Inui A, Hu Z, Han G, et al. Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile. Endocrinology. 2008 Feb;149(2):827-35

  86. 86.Ashby DR, For HE, Wynne KJ, Wren AM, Murphy KG, Busbridge M, et al. Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment. Kidney Int. 2009 Jul;76(2):199-206.

  87. 87.Kangawa K. Challenge for novel peptide hormones: from discovery to therapeutic application. Endocr J. 2009;56(9): 1031-2

  88. 88.Dixit VD, Schaffer EM, Pyle RS, Collings GD, Sakthivel SK, Palaniappan R, et al. Ghrelin inhibits leptin-and activation- induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest. 2004 Jul;114(1):57-66.

  89. 89.Nagaya N, Miyatake K, Uematsu M, Oya H, Shimizu W, Hosoda H, et al. Hemodynamic, renal, and hormonal effects of ghrelin infusión in patients with chronic heart failure. J Clin Endocrinol Metab. 2001 Dec;86(12):5854-9.

  90. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, et al. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endotelial cells through ERK1/2 and PI 3- kinase/AKT. J Cell Biol. 2002 Dec 23;159(6):1029- 37.

  91. 91.Tena-Sempere M. Ghrelin, the gonadal axis and the onset of puberty. Endocr Dev. 2013;25:69-82.

  92. 92.Dun SL, Brailoui GC, Brailoui E, Yang J, Chang JK, Dun NJ. Distribution and biological activity of obestatin in the rat. J Endocrinol. 2006 Nov;191(2):481-9.

  93. 93.Li JB, Asakawa A, Cheng K, Li Y, Chaolu H, Tsai M, Inui A. Biological effects of obestatin. Endocrine. 2011 Jun;39(3):205-11.

  94. 94.Tang SQ, Jiang QY, Zhang YL, Zhu XT, Shu G, Gao P, et al. Obestatin: its physicochemical characteristics and physiological functions. Peptides. 2008 Apr;29(4):639-45.

  95. 95.Green BD, Irwin N, Flatt PR. Direct and indirect effects of obestatin peptides on food intake and the regulation of glucose homeostasis and insulin secretion in mice. Peptides. 2007 May;28(5):981-7.

  96. 96.Nogueiras R, Pfluger P, Tovar S, Arnold M, Mitchell S, Morris A, et al. Effects of obestatin on energy balance and growth hormone secretion in rodents. Endocrinology. 2007 Jan;148(1):21-6.

  97. 97.Egido EM, Hernández R, Marco J, Silvestre RA. Effect of obestatin on insulin, glucagón and somatostatin secretion in the perfused rat páncreas. Regul Pept. 2009 Jan 8; 152(1-3):61-6.

  98. 98.Dun SL, Brailoui GC, Brailoiu E, Yang J, Chang JK, Dun NJ. Distribution and biological activity of obestatinin therat. J Endocrinol. 2006 Nov;191(2):481-9.

  99. 99.Garg A. The ongoing saga of obestatin: is it a hormone? J Clin Endocrinol Metab. 2007 Sep;92(9):3396-8.

  100. 100.Seim I, Josh P, Cunningham P, Herington A, Chopin L. Ghrelin axis genes, peptides and receptors: recent findings and future challenges. Mol Cell Endocrinol. 2011 Jun 20;340(1):3-9.

  101. 101.Bresciani E, Rapetti D, et al. Obestatin inhibits feedingbut does not modulate GHand corticosterone secretion in the rat. J Endocrinol Invest. 2006 Sep;29(8):RC16-8.

  102. 102.Zamrazilová H, et al. Physiol Res. 2008;57 Suppl 1:S49-55.

  103. Granata R, Volante M, et al. Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats. J Mol Endocrinol. 2010 Jul;45(1):9-17

  104. 104 Benso A, Casanueva FF, Ghigo E, Granata A. The Ghrelun System. Endocr Dev. Basel, Karger, 2013, vol 25, pp 16-24.




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