Ghrelin in diabetes andmetabolic syndrome

International Journal of Peptides

Volumn 2010, Issue , 2010, Pages

  Pulkkinen, Leena ^a   Ukkola, Olavi ^b   Kolehmainen, Marjukka ^a   Uusitupa, Matti ^a  

^a UNIVERSITY OF EASTERN FINLAND   (Finland)

^b UNIVERSITY OF OULU   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

GHRELIN;

APPETITE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; ENERGY BALANCE; GENETIC ASSOCIATION; GENOTYPE ENVIRONMENT INTERACTION; HUMAN; LIVER DISEASE; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PRIORITY JOURNAL; PUBLIC HEALTH PROBLEM; REVIEW;

EID: 84871065188     PISSN: 16879767     EISSN: 16879775     Source Type: Journal    
DOI: 10.1155/2010/248948     Document Type: Review

References (128)

1. O. Ukkola, Ghrelin and metabolic disorders, Current Protein and Peptide Science, vol. 10, no. 1, pp. 2-7, 2009.
2. S. M. P̈oykk̈o, E. Kellokoski, S. Ḧorkk̈oe, H. Kauma, Y. A. Kes̈aniemi, and O. Ukkola, Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes, Diabetes, vol. 52, no. 10, pp. 2546-2553, 2003. (Pubitemid 37210544)
3. R. Barazzoni, M. Zanetti, C. Ferreira, et al., Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome, Journal of Clinical Endocrinology and Metabolism, vol. 92, pp. 3935-3940, 2007. (Pubitemid 47607644)
4. M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, and K. Kangawa, Ghrelin is a growth-hormone-releasing acylated peptide from stomach, Nature, vol. 402, no. 6762, pp. 656-660, 1999. (Pubitemid 129516334)
5. M. Tscḧop, C. Weyer, P. A. Tataranni, V. Devanarayan, E. Ravussin, and M. L. Heiman, Circulating ghrelin levels are decreased in human obesity, Diabetes, vol. 50, no. 4, pp. 707-709, 2001. (Pubitemid 32242624)
6. D. Vivenza, A. Rapa, N. Castellino, et al., Ghrelin gene polymorphisms and ghrelin, insulin, IGF-I, leptin and anthropometric data in children and adolescents, European Journal of Endocrinology, vol. 151, no. 1, pp. 127-133, 2004. (Pubitemid 39117375)
7. T. Shiiya, M. Nakazato, M. Mizuta, et al., Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion, Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 1, pp. 240-244, 2002. (Pubitemid 34084697)
8. T. Ostergard, T. K. Hansen, B. Nyholm, et al., Circulating ghrelin concentrations are reduced in healthy offspring of type 2 diabetic subjects, and are increased in women independent of a family history of type 2 diabetes, Diabetologia, vol. 46, no. 1, pp. 134-136, 2003. (Pubitemid 36237757)
9. M. Tscḧop, R. Wawarta, R. L. Riepl, et al., Post-prandial decrease of circulating human ghrelin levels, Journal of Endocrinological Investigation, vol. 24, no. 6, pp. RC19-RC21, 2001. (Pubitemid 32573786)
10. P. J. English, M. A. Ghatei, I. A. Malik, S. R. Bloom, and J. P. H. Wilding, Food fails to suppress ghrelin levels in obese humans, Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 6, pp. 2984-2987, 2002. (Pubitemid 34655374)
11. S. C. Higgins, M. Gueorguiev, and M. Korbonits, Ghrelin, the peripheral hunger hormone, Annals of Medicine, vol. 39, no. 2, pp. 116-136, 2007. (Pubitemid 46598179)
12. O. Ukkola, S. M. P̈oykk̈o, and Y. A Kes̈aniemi, Low plasma ghrelin concentration is an indicator of themetabolic syndrome, Journal of Clinical Endocrinology & Metabolism, vol. 90, pp. 6448-6453, 2005.
13. C. Langenberg, J. Bergstrom, G. A. Laughlin, and E. Barrett-Connor, Ghrelin and the metabolic syndrome in older adults, Journal of Clinical Endocrinology andMetabolism, vol. 90, no. 12, pp. 6448-6453, 2005. (Pubitemid 41759298)
14. T. McLaughlin, F. Abbasi, C. Lamendola, R. S. Frayo, and D. E. Cummings, Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive contrls, Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 4, pp. 1630-1635, 2004. (Pubitemid 38507912)
15. D. H. St-Pierre, A. D. Karelis, L. Coderre, et al., Association of acylated and nonacylated ghrelin with insulin sensitivity in overweight and obese postmenopausal women, Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 1, pp. 264-269, 2007. (Pubitemid 46067542)
16. R. S. Legro, A. R. Kunselman, W. C. Dodson, and A. Dunaif, Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women, Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 1, pp. 165-169, 1999. (Pubitemid 29036695)
17. S. Franks, Polycystic ovary syndrome, The New England Journal of Medicine, vol. 333, pp. 853-861, 1995.
18. U. Pagotto, A. Gambineri, V. Vicennati, M. L. Heiman, M. Tschop, and R. Pasquali, Plasma ghrelin, obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels, Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 12, pp. 5625-5629, 2002. (Pubitemid 36034369)
19. C. Scḧofl, R. Horn, T. Schill, H. W. Schl̈osser, M. J. Müller, and G. Brabant, Circulating ghrelin levels in patients with polycystic ovary syndrome, Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 10, pp. 4607-4610, 2002. (Pubitemid 35247048)
20. F. Orio Jr., P. Lucidi, S. Palomba, et al., Circulating ghrelin concentrations in the polycystic ovary syndrome, Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 2, pp. 942-945, 2003. (Pubitemid 36207846)
21. D. E. Cummings, D. S. Weigle, R. S. Frayo, et al., Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery, The New England Journal of Medicine, vol. 346, no. 21, pp. 1623-1630, 2002. (Pubitemid 34755670)
22. S. Santosa, I. Demonty, A. H. Lichtenstein, K. Cianflone, and P. J. H. Jones, An investigation of hormone and lipid associations after weight loss in women, Journal of the American College of Nutrition, vol. 26, no. 3, pp. 250-258, 2007. (Pubitemid 47124375)
23. D. S. Weigle, D. E. Cummings, P. D. Newby, et al., Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet, Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 4, pp. 1577-1586, 2003. (Pubitemid 36623373)
24. T. Reinehr, G. de Sousa, and C. L. Roth, Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight, Clinical Endocrinology, vol. 68, no. 2, pp. 304-310, 2007.
25. J. M. Garcia, D. Iyer, W. S. C. Poston, et al., Rise of plasma ghrelin with weight loss is not sustained during weight maintenance, Obesity, vol. 14, no. 10, pp. 1716-1723, 2006. (Pubitemid 46214793)
26. M. P. G. M. Lejeune, C. J. Hukshorn, W. H. M. Saris, and M. S. Westerterp-Plantenga, Effects of very low calorie diet induced body weight loss with or without human pegylated recombinant leptin treatment on changes in ghrelin and adiponectin concentrations, Physiology and Behavior, vol. 91, no. 2-3, pp. 274-280, 2007. (Pubitemid 46770807)
27. H. J. Leidy, K. A. Dougherty, B. R. Frye, K.M. Duke, and N. I. Williams, Twenty-four-hour ghrelin is elevated after calorie restriction and exercise training in non-obese women, Obesity, vol. 15, no. 2, pp. 446-455, 2007. (Pubitemid 46407326)
28. H. J. Kim, S. Lee, T. W. Kim, et al., Effects of exerciseinduced weight loss on acylated and unacylated ghrelin in overweight children, Clinical Endocrinology, vol. 68, no. 3, pp. 416-422, 2008. (Pubitemid 351257861)
29. T. Reinehr, C. L. Roth, U. Alexy, M. Kersting, W. Kiess, and W. Andler, Ghrelin levels before and after reduction of overweight due to a low-fat high-carbohydrate diet in obese children and adolescents, International Journal of Obesity, vol. 29, no. 4, pp. 362-368, 2005. (Pubitemid 40462757)
30. E. Ravussin, M. Tscḧop, S. Morales, C. Bouchard, and M. L. Heiman, Plasma ghrelin concentration and energy balance: overfeeding and negative energy balance studies in twins, Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 9, pp. 4547-4551, 2001. (Pubitemid 32848587)
31. M. F. Saad, B. Bernaba, C.-M. Hwu, et al., Insulin regulates plasma ghrelin concentration, Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 8, pp. 3997-4000, 2002. (Pubitemid 34879561)
32. M. O. Weickert, C. V. Loeffelholz, A. M. Arafat, et al., Euglycemic hyperinsulinemia differentially modulates circulating total and acylated-ghrelin in humans, Journal of Endocrinological Investigation, vol. 31, no. 2, pp. 119-124, 2008. (Pubitemid 351596971)
33. F. Broglio, C. Gottero, F. Prodam, et al., Ghrelin secretion is inhibited by glucose load and insulin-induced hypoglycaemia but unaffected by glucagon and arginine in humans, Clinical Endocrinology, vol. 61, no. 4, pp. 503-509, 2004. (Pubitemid 39388490)
34. G.Murdolo, P. Lucidi, C. Di Loreto, et al., Insulin is required for prandial ghrelin suppression in humans, Diabetes, vol. 52, no. 12, pp. 2923-2927, 2003. (Pubitemid 37466861)
35. F. Broglio, A. Benso, C. Gottero, et al., Effects of glucose, free fatty acids or arginine load on the GH-releasing activity of ghrelin in humans, Clinical Endocrinology, vol. 57, no. 2, pp. 265-271, 2002. (Pubitemid 34989104)
36. L. Briatore, G. Andraghetti, and R. Cordera, Acute plasma glucose increase, but not early insulin response, regulates plasma ghrelin, European Journal of Endocrinology, vol. 149, no. 5, pp. 403-406, 2003. (Pubitemid 37461520)
37. D. E. Flanagan, M. L. Evans, T. P. Monsod, et al., The influence of insulin on circulating ghrelin, American Journal of Physiology, vol. 284, no. 2, pp. E313-E316, 2003. (Pubitemid 36120103)
38. J. Liu, C. E. Prudom, R. Nass, et al., Novel ghrelin assays provide evidence for independent regulation of ghrelin acylation and secretion in healthy young men, Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 5, pp. 1980-1987, 2008. (Pubitemid 351656547)
39. G. Schaller, A. Schmidt, J. Pleiner, et al., Plasma ghrelin concentrations are not regulated by glucose or insulin: a doubleblind, placebo controlled crossover clamp study, Diabetes, vol. 52, article 1620, 2003.
40. Broglio, 2001.
41. Y. Greenman, N. Golani, S. Gilad, M. Yaron, R. Limor, and N. Stern, Ghrelin secretion is modulated in a nutrient-and gender-specific manner, Clinical Endocrinology, vol. 60, no. 3, pp. 382-388, 2004. (Pubitemid 38297130)
42. R. M. Kiewiet, M. O. van Aken, K. van der Weerd, et al., Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes, European Journal of Endocrinology, vol. 161, no. 4, pp. 567-573, 2009.
43. M. Nakazato, N.Murakami, Y. Date, et al., A role for ghrelin in the central regulation of feeding, Nature, vol. 409, no. 6817, pp. 194-198, 2001. (Pubitemid 32144284)
44. F. Broglio, E. Arvat, A. Benso, et al., Ghrelin, a natural gh secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans, Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 10, pp. 5083-5086, 2001. (Pubitemid 33020569)
45. F. Broglio, C. Gottero, A. Benso, et al., Effects of ghrelin on the insulin and glycemic responses to glucose, arginine, or free fatty acids load in humans, Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 9, pp. 4268-4272, 2003. (Pubitemid 37153730)
46. M. Arosio, C. L. Ronchi, C. Gebbia, V. Cappiello, P. Beck-Peccoz, and M. Peracchi, Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels, Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 2, pp. 701-704, 2003. (Pubitemid 36207811)
47. F. Broglio, F. Prodam, F. Riganti, et al., The continuous infusion of acylated ghrelin enhances growth hormone secretion and worsens glucose metabolism in humans, Journal of Endocrinological Investigation, vol. 31, no. 9, pp. 788-794, 2008.
48. C. Gauna, F. M. Meyler, J. A. Janssen, et al., Administration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity, Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 10, pp. 5035-5042, 2004. (Pubitemid 39391445)
49. C. Gauna, P. J. D. Delhanty, L. J. Hofland, et al., Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes, Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 2, pp. 1055-1060, 2005. (Pubitemid 40279233)
50. S. M. P̈oykk̈o, E. Kellokoski, S. Ḧorkk̈o, H. Kauma, Y. A. Kes̈aniemi, and O. Ukkola, Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes, Diabetes, vol. 52, no. 10, pp. 2546-2553, 2003. (Pubitemid 37210544)
51. F. Broglio, C. Gottero, F. Prodam, et al., Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans, Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 6, pp. 3062-3065, 2004. (Pubitemid 38766409)
52. R. Granata, F. Settanni, L. Biancone, et al., Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic betacells 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, vol. 148, no. 2, pp. 512-529, 2007. (Pubitemid 46143157)
53. C. Gauna, P. J. Delhanty, M. O. van Aken, et al., Unacylated ghrelin is active on the INS-1E rat insulinoma cell line independently of the growth hormone secretagogue receptor type 1a and the corticotropin releasing factor 2 receptor, Molecular and Cellular Endocrinology, vol. 251, pp. 103-111, 2006. (Pubitemid 43728835)
54. M. Murata, Y. Okimura, K. Iida, et al., Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells, Journal of Biological Chemistry, vol. 277, no. 7, pp. 5667-5674, 2002. (Pubitemid 34968622)
55. K. M. Andralojc, A. Mercalli, K. W. Nowak, et al., Ghrelinproducing epsilon cells in the developing and adult human pancreas, Diabetologia, vol. 52, no. 3, pp. 486-493, 2009.
56. C. L. Prado, A. E. Pugh-Bernard, L. Elghazi, B. Sosa-Pineda, and L. Sussel, Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development, Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 9, pp. 2924-2929, 2004. (Pubitemid 38327712)
57. R. S. Heller, M. Jenny, P. Collombat, et al., Genetic determinants of pancreatic epsilon-cell development, Developmental Biology, vol. 286, no. 1, pp. 217-224, 2005. (Pubitemid 41394059)
58. A. Salehi, C. D. De La Cour, R. Hakanson, and I. Lundquist, Effects of ghrelin on insulin and glucagon secretion: a study of isolated pancreatic islets and intact mice, Regulatory Peptides, vol. 118, no. 3, pp. 143-150, 2004. (Pubitemid 38296727)
59. S. S. Qader, R. Hakanson, J. F. Rehfeld, I. Lundquist, and A. Salehi, Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas, Regulatory Peptides, vol. 146, no. 1-3, pp. 230-237, 2008.
60. R. Granata, F. Settanni, L. Trovato, et al., Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HITT15 pancreatic beta cells, Journal of Endocrinological Investigation, vol. 29, article RC1922, 2006.
61. T. Yada, K. Dezaki, H. Sone, et al., Ghrelin regulates insulin release and glycemia: physiological role and therapeutic potential, Current Diabetes Reviews, vol. 4, no. 1, pp. 18-23, 2008. (Pubitemid 351210968)
62. K. Rabe, M. Lehrke, K. G. Parhofer, and U. C. Broedl, Adipokines and insulin resistance, Molecular Medicine, vol. 14, no. 11-12, pp. 741-751, 2008.
63. M. Tschöp, D. L. Smiley, and M. L. Heiman, Ghrelin induces adiposity in rodents, Nature, vol. 407, no. 6806, pp. 908-913, 2000.
64. A. Rodŕ?guez, J. Ǵomez-Ambrosi, V. Cataĺan, et al., Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes, International Journal of Obesity, vol. 33, no. 5, pp. 541-552, 2009.
65. M. S. Kim, C. Y. Yoon, P. G. Jang, et al., The mitogenic and antiapoptotic actions of ghrelin in 3T3L1 adipocytes, Molecular Endocrinology, vol. 18, pp. 2291-2301, 2004.
66. B. Kola, A. Grossman, and M. Korbonits, The role of AMPactivated protein kinase in obesity, Frontiers of Hormone Research, vol. 36, pp. 198-211, 2008.
67. G. Muccioli, N. Pons, C. Ghe, F. Catapano, R. Granata, and E. Ghigo, Ghrelin and desacyl ghrelin both inhibit isoproterenolinduced lipolysis in rat adipocytes via a nontype 1a growth hormone secretagogue receptor, European Journal of Pharmacology, vol. 498, pp. 27-35, 2004. (Pubitemid 39208057)
68. T. Tsubone, T. Masaki, I. Katsuragi, K. Tanaka, T. Kakuma, and H. Yoshimatsu, Ghrelin regulates adiposity in white adipose tissue and UCP1 mRNA expression in brown adipose tissue in mice, Regulatory Peptides, vol. 130, no. 1-2, pp. 97-103, 2005. (Pubitemid 40966028)
69. N. M. Thompson, D. A. Gill, R. Davies, et al., Ghrelin and desoctanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor, Endocrinology, vol. 145, pp. 234-242, 2004. (Pubitemid 38202164)
70. A. Mano-Otagiri, H. Ohata, A. Iwasaki-Sekino, T. Nemoto, and T. Shibasaki, Ghrelin suppresses noradrenaline release in the brown adipose tissue of rats, Journal of Endocrinology, vol. 201, no. 3, pp. 341-349, 2009.
71. K. Choi, S.-G. Roh, Y.-H. Hong, et al., The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis, Endocrinology, vol. 144, no. 3, pp. 754-759, 2003. (Pubitemid 36262842)
72. O. Ukkola, E. Ravussin, P. Jacobson, et al., Mutations in the preproghrelin/ghrelin gene associated with obesity in humans, Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 8, pp. 3996-3999, 2001. (Pubitemid 32756010)
73. O. Ukkola, E. Ravussin, P. Jacobson, et al., Role of Ghrelin polymorphisms in obesity based on three different studies, Obesity Research, vol. 10, no. 8, pp. 782-791, 2002. (Pubitemid 135687519)
74. M. Korbonits, M. Gueorguiev, E. OGrady, et al., A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children, Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 8, pp. 4005-4008, 2002. (Pubitemid 34879563)
75. A. Hinney, A. Hoch, F. Geller, et al., Ghrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students, Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 6, pp. 2716-2719, 2002. (Pubitemid 34655335)
76. O. Ukkola and Y. A. Kes̈aniemi, Preproghrelin Leu72Met polymorphism in patients with type 2 diabetes mellitus, Journal of Internal Medicine, vol. 254, no. 4, pp. 391-394, 2003. (Pubitemid 37211263)
77. S. P̈oykk̈o, O. Ukkola, H. Kauma, M. J. Savolainen, and Y. A. Kes̈aniemi, Ghrelin Arg51Gln mutation is a risk factor for type 2 diabetes and hypertension in a random sample of middle-aged subjects, Diabetologia, vol. 46, no. 4, pp. 455-458, 2003. (Pubitemid 36577786)
78. D. R. Skibola, M. T. Smith, P. M. Bracci, et al., Polymorphisms in ghrelin and neuropeptide Y genes are associated with non-Hodgkin lymphoma, Cancer Epidemiology Biomarkers and Prevention, vol. 14, no. 5, pp. 1251-1256, 2005. (Pubitemid 40656476)
79. N. I. Steinle, T. I. Pollin, J. R. OConnell, B. D. Mitchell, and A. R. Shuldiner, Variants in the ghrelin gene are associated with metabolic syndrome in the Old Order Amish, Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 12, pp. 6672-6677, 2005. (Pubitemid 41759331)
80. S. J. Yoon, C. U. Pae, H. Lee, et al., Ghrelin precursor gene polymorphism and methamphetamine dependence in the Korean population, Neurosci Res., vol. 53, no. 4, pp. 391-395, 2005. (Pubitemid 41643066)
81. D.-S. Jo, S.-L. Kim, S.-Y. Kim, P. H. Hwang, K.-H. Lee, and D.-Y. Lee, Preproghrelin Leu72Met polymorphism in obese Korean children, Journal of Pediatric Endocrinology and Metabolism, vol. 18, no. 11, pp. 1083-1086, 2005. (Pubitemid 43019996)
82. H. J. Choi, Y. M. Cho, M. K. Moon, et al., Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans, Journal of Clinical Endocrinology and Metabolism, vol. 91, pp. 4657-4563, 2006.
83. S. Zavarella, A. Petrone, S. Zampetti, et al., A new variation in the promoter region, the 604 > T, and the Leu72Met polymorphism of the ghrelin gene are associated with protection to insulin resistance, International Journal of Obesity, vol. 32, no. 4, pp. 663-668, 2008. (Pubitemid 351536011)
84. D.-Y. Lee, S.-Y. Kim, D.-S. Jo, et al., Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy, European Journal of Endocrinology, vol. 155, no. 1, pp. 187-190, 2006. (Pubitemid 44103388)
85. J. Vartiainen, Y. A. Kes̈aniemi, and O. Ukkola, Sequencing analysis of ghrelin gene 5′ flanking region: relations between the sequence variants, fasting plasma total ghrelin concentrations, and body mass index, Metabolism, vol. 55, no. 10, pp. 1420-1425, 2006. (Pubitemid 44353562)
86. T. I. Sørensen, P. Boutin, and M. A. Taylor, Genetic polymorphisms and weight loss in obesity: a randomised trial of hypo-energetic high-versus low-fat diets, PLoS Clinical Trials, vol. 1, no. 2, article e12, 2006.
87. M. Kuzuya, F. Ando, A. Iguchi, and H. Shimokata, Preproghrelin Leu72Met variant contributes to overweight in middleaged men of a Japanese large cohort, International Journal of Obesity, vol. 30, pp. 1609-1614, 2006. (Pubitemid 44657834)
88. N.-P. Tang, L.-S. Wang, L. Yang, et al., Preproghrelin Leu72Met polymorphism in Chinese subjects with coronary artery disease and controls, Clinica Chimica Acta, vol. 387, no. 1-2, pp. 42-47, 2008. (Pubitemid 350050926)
89. T. Ando, Y. Ichimaru, F. Konjiki, M. Shoji, and G. Komaki, Variations in the preproghrelin gene correlate with higher body mass index, fat mass, and body dissatisfaction in young Japanese women, American Journal of Clinical Nutrition, vol. 86, no. 1, pp. 25-32, 2007. (Pubitemid 47041589)
90. J. A. Hubacek, S. Bloud́?ckov́a, R. Bohuslavov́a, et al., Ghrelin variants influence development of body mass index and plasma levels of total cholesterol in dialyzed patients, Clinical Chemistry and Laboratory Medicine, vol. 45, no. 9, pp. 1121-1123, 2007. (Pubitemid 47396258)
91. U. Mager, V. Lindi, J. Lindstr̈om, et al., Association of the Leu72Met polymorphism of the ghrelin gene with the risk of type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study, Diabetic Medicine, vol. 23, no. 6, pp. 685-689, 2006. (Pubitemid 43830072)
92. U. Mager, M. Kolehmainen, J. Lindstr̈om, et al., Association between ghrelin gene variations and blood pressure in subjects with impaired glucose tolerance, American Journal of Hypertension, vol. 19, no. 9, pp. 920-926, 2006. (Pubitemid 46106998)
93. W. Zhang, L. Zhao, T. R. Lin, et al., Inhibition of adipogenesis by ghrelin, Molecular Biology of the Cell, vol. 15, no. 5, pp. 2484-2491, 2004. (Pubitemid 38580662)
94. V. Ott, M. Fasshauer, A. Dalski, et al., Direct peripheral effects of ghrelin include suppression of adiponectin expression, Hormone and Metabolic Research, vol. 34, no. 11-12, pp. 640-645, 2002. (Pubitemid 36398699)
95. A. Giovambattista, J. Piermaria, M. O. Suescun, R. S. Calandra, R. C. Gaillard, and E. Spinedi, Direct effect of ghrelin on leptin production by cultured rat white adipocytes, Obesity, vol. 14, no. 1, pp. 19-27, 2006. (Pubitemid 46214771)
96. V. D. Dixit and D. D. Taub, Ghrelin and immunity: a young player in an old field, Experimental Gerontology, vol. 40, no. 11, pp. 900910, 2005. (Pubitemid 41540440)
97. M. Papotti, C. Ghe, P. Cassoni, et al., Growth hormone secretagogue binding sites in peripheral human tissues, Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 10, pp. 3803-3807, 2000.
98. M. Tesauro, F. Schinzari, M. Iantorno, et al., Ghrelin improves endothelial function in patients with metabolic syndrome, Circulation, vol. 112, no. 19, pp. 2986-2992, 2005. (Pubitemid 41612302)
99. M. Tesauro, F. Schinzari, V. Rovella, et al., Ghrelin restores the endothelin 1/nitric oxide balance in patients with obesity-related metabolic syndrome, Hypertension, vol. 54, no. 5, pp. 995-1000, 2009.
100. J.-M. Cao, H. Ong, and C. Chen, Effects of ghrelin and synthetic GH secretagogues on the cardiovascular system, Trends in Endocrinology and Metabolism, vol. 17, no. 1, pp. 13-18, 2006. (Pubitemid 43031379)
101. H. Okumura, N. Nagaya, M. Enomoto, E. Nakagawa, H. Oya, and K. Kangawa, Vasodilatory effect of ghrelin, an endogenous peptide from the stomach, Journal of Cardiovascular Pharmacology, vol. 39, no. 6, pp. 779-783, 2002. (Pubitemid 34538806)
102. N. Nagaya and K. Kangawa, Therapeutic potential of ghrelin in the treatment of heart failure, Drugs, vol. 66, no. 4, pp. 439-448, 2006.
103. N. Nagaya, M. Uematsu, M. Kojima, et al., Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure, Circulation, vol. 104, no. 12, pp. 1430-1435, 2001. (Pubitemid 32880158)
104. S. M. P̈oykk̈o, E. Kellokoski, O. Ukkola, et al., Plasma ghrelin concentrations are positively associated with carotid artery atherosclerosis in males, Journal of Internal Medicine, vol. 260, no. 1, pp. 43-52, 2006. (Pubitemid 43894069)
105. A. Fernandez, I. Kaczmarek, M. Schmoeckel, A. Beiras, C. Vicol, and B. Reichart, Expression of Ghrelin, a novel cardiovascular hormone, and its peptide in the myocardium of patients undergoing heart transplantation, The Journal of Heart and Lung Transplantation, vol. 2, no. 1, supplement 1, pp. S84-S85, 2007.
106. X. Xu, B. S. Jhun, C. H. Ha, and Z. G. Jin, Molecular mechanisms of ghrelin-mediated endothelial nitric oxide synthase activation Endocrinology, Endocrinology, vol. 149, pp. 4183-4192, 2008.
107. G. Togliatto, A. Trombetta, and P. Dentelli, Unacylated ghrelin rescues endothelial progenitor cell function in individuals with type 2 diabetes, Diabetes, vol. 59, no. 4, pp. 1016-1025, 2010.
108. M. Tesauro, F. Schinzari, V. Rovella, et al., Ghrelin restores the endothelin 1/nitric oxide balance in patients with obesity-related metabolic syndrome, Hypertension, vol. 54, no. 5, pp. 995-1000, 2009.
109. J. Yang, M. S. Brown, G. Liang, N. V. Grishin, and J. L. Goldstein, Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone, Cell, vol. 132, no. 3, pp. 387-396, 2008. (Pubitemid 351192001)
110. J. A. Gutierrez, P. J. Solenberg, D. R. Perkins, et al., Ghrelin octanoylation mediated by an orphan lipid transferase, Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 17, pp. 6320-6325, 2008. (Pubitemid 351758344)
111. I. Sakata, J. Yang, C. E. Lee, et al., Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells, American Journal of Physiology, vol. 297, no. 1, pp. E134-E141, 2009.
112. H. Kirchner, J. A. Gutierrez, P. J. Solenberg, et al., GOAT links dietary lipids with the endocrine control of energy balance, Nature Medicine, vol. 15, no. 7, pp. 741-745, 2009.
113. H. Kirchner, J. A. Gutierrez, P. J. Solenberg, et al., Erratum: GOAT links dietary lipids with the endocrine control of energy balance (Nature Medicine (2009) 15 (741-745)), Nature Medicine, vol. 15, no. 9, p. 1093, 2009.
114. A. Moulin, L. Demange, G. Berǵe, et al., Toward potent ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure. 2. Synthesis and pharmacological in vitro and in vivo evaluations, Journal of Medicinal Chemistry, vol. 50, no. 23, pp. 5790-5806, 2007. (Pubitemid 350106034)
115. O. Gualillo, F. Lago, and C. Dieguez, Introducing GOAT: a target for obesity and anti-diabetic drugs? Trends in Pharmacological Sciences, vol. 29, no. 8, pp. 398-401, 2008.
116. H. Schellekens, T. G. Dinan, and J. F. Cryan, Lean mean fat reducing ghrelin machine: hypothalamic ghrelin and ghrelin receptors as therapeutic targets in obesity, Neuropharmacology, vol. 58, no. 1, pp. 2-16, 2010.
117. W. P. Esler, J. Rudolph, T. H. Claus, et al., Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss, Endocrinology, vol. 148, no. 11, pp. 5175-5185, 2007. (Pubitemid 350012622)
118. S.-C. Lu, J. Xu, N. Chinookoswong, et al., An acylghrelin-specific neutralizing antibody inhibits the acute ghrelin-mediated orexigenic effects in mice, Molecular Pharmacology, vol. 75, no. 4, pp. 901-907, 2009.
119. E. P. Zorrilla, S. Iwasaki, J. A. Moss, et al., Vaccination against weight gain, Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 35, pp. 13226-13231, 2006. (Pubitemid 44338944)
120. L. P. Shearman, S.-P. Wang, S. Helmling, et al., Ghrelin neutralization by a ribonucleic acid-SPM ameliorates obesity in diet-induced obese mice, Endocrinology, vol. 147, no. 3, pp. 1517-1526, 2006. (Pubitemid 43244387)
121. C. Becskei, K. U. Bilik, S. Klussmann, F. Jarosch, T. A. Lutz, and T. Riediger, The anti-ghrelin spiegelmer NOXB11-blocks ghrelin-but not fasting-induced neuronal activation in the hypothalamic arcuate nucleus blocks Journal of Neuroendocrinology, vol. 20, no. 1, pp. 85-92, 2008. (Pubitemid 350239152)
122. X. Wu, R. S. Cooper, E. Boerwinkle, et al., Combined analysis of genomewide scans for adult height: results from the NHLBI family blood pressure program, European Journal of Human Genetics, vol. 11, no. 3, pp. 271-274, 2003. (Pubitemid 36511865)
123. A. H. Kissebah, G. E. Sonnenberg, J. Myklebust, et al., Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome, Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 26, pp. 14478-14483, 2000. (Pubitemid 32016601)
124. E. Miraglia del Giudice, N. Santoro, G. Cirillo, et al., Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity, International Journal of Obesity, vol. 28, no. 3, pp. 447-450, 2004. (Pubitemid 38296960)
125. C. Bing, L. Ambye, M. Fenger, et al., Large-scale studies of the Leu72Met polymorphism of the ghrelin gene in relation to the metabolic syndrome and associated quantitative traits, DiabeticMedicine, vol. 22, no. 9, pp. 1157-1160, 2005. (Pubitemid 41224173)
126. L. H. Larsen, A. P. Gjesing, T. I. A. Sørensen, et al., Mutation analysis of the preproghrelin gene: no association with obesity and type 2 diabetes, Clinical Biochemistry, vol. 38, no. 5, pp. 420-424, 2005.
127. J. Vartiainen, S. M. P̈oykk̈o, T. R̈ais̈anen, Y. A. Kes̈aniemi, and O. Ukkola, Sequencing analysis of the ghrelin receptor (growth hormone secretagogue receptor type 1a) gene, European Journal of Endocrinology, vol. 150, no. 4, pp. 457-463, 2004. (Pubitemid 38584695)
128. U. Mager, T. Degenhardt, L. Pulkkinen, et al., Variations in the ghrelin receptor gene associate with obesity and glucose metabolism in individuals with impaired glucose tolerance, PLoS One, vol. 3, no. 8, article e2941, 2008.