Ghrelin, an acylated 28-amino-acid peptide, is an endogenous ligand of the growth hormone secretagogue type 1a (GHS-R1a). Ghrelin is best known for its hypothalamic actions on growth hormone-releasing hormone neurons and neuropeptide Y/agouti-related peptide neurons; however, ghrelin affects multiple organ systems and the complexity of its functions is only now being realized. Although ghrelin is mainly produced in the stomach, it is also produced in low levels by the hypothalamus and by most peripheral tissues. GHS-R1a is expressed predominantly in the anterior pituitary gland, at lower levels in the brain including hypothalamic neurons that regulate feeding behavior and glucose sensing, and at even lower levels in the pancreas. A reciprocal relationship exists between ghrelin and insulin, suggesting that ghrelin regulates glucose homeostasis. Ablation of ghrelin in mice increases glucose-induced insulin secretion, and improves peripheral insulin sensitivity. This review focuses on the newly emerging role of ghrelin in glucose homeostasis and exploration of whether ghrelin is a potential therapeutic target for diabetes.

Keywords:
Ghrelin, GHS-R, Pancreas, Diabetes, Glucose homeostasis, Insulin resistance, Leptin
1.
Smith RG, Pong S-S, Hickey GJ, Jacks TM, Cheng K, Leonard RJ, Cohen CJ, Arena JP, Chang CH, Drisko JE, Wyvratt MJ Jr, Fisher MH, Nargund RP, Patchett AA: Modulation of pulsatile GH release through a novel receptor in hypothalamus and pituitary gland. Recent Prog Horm Res 1996;51:261–286.
2.
Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, McKee KK, Pong S-S, Chaung L-YP, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJS, Dean DC, Melillo DG, Patchett AA, Nargund RP, Griffin PR, DeMartino JA, Gupta SK, Schaeffer JM, Smith RG, Van der Ploeg LHT: A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996;273:974–977.
3.
Smith RG, Van der Ploeg LH, Howard AD, Feighner SD, Cheng K, Hickey GJ, Wyvratt MJ Jr, Fisher MH, Nargund RP, Patchett AA: Peptidomimetic regulation of growth hormone secretion. Endocr Rev 1997;18:621–645.
4.
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.
5.
Peino R, Baldelli R, Rodriguez-Garcia J, Rodriguez-Segade S, Kojima M, Kangawa K, Arvat E, Ghigo E, Dieguez C, Casanueva FF: Ghrelin-induced growth hormone secretion in humans. Eur J Endocrinol 2000;143:R11–R14.
6.
Hataya Y, Akamizu T, Takaya K, Kanamoto N, Ariyasu H, Saijo M, Moriyama K, Shimatsu A, Kojima M, Kangawa K, Nakao K: A low dose of ghrelin stimulates GH release synergistically with GH-releasing hormone in humans. J Clin Endocrinol Metab 2001;86:4552.
7.
Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S: A role for ghrelin in the central regulation of feeding. Nature 2001;409:194–198.
8.
Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA, Batterham RL, Taheri S, Stanley SA, Ghatei MA, Bloom SR: Ghrelin causes hyperphagia and obesity in rats. Diabetes 2001;50:2540–2547.
9.
Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR: Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001;86:5992.
10.
Smith RG: Development of growth hormone secretagogues. Endocr Rev 2005;26:346–360.
11.
Smith RG, Jiang H, Sun Y: Developments in ghrelin biology and potential clinical relevance. Trends Endocrinol Metab 2005;16:436–442.
12.
Broglio F, Prodam F, Me E, Riganti F, Lucatello B, Granata R, Benso A, Muccioli G, Ghigo E: Ghrelin: Endocrine, metabolic and cardiovascular actions. J Endocrinol Invest 2005;28:23–25.
13.
Sun Y, Wang P, Zheng H, Smith RG: Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci USA 2004;101:4679–4684.
14.
Sun Y, Ahmed S, Smith RG: Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol 2003;23:7973–7981.
15.
Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJ: Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 2005;310:996–999.
16.
Broglio F, Gottero C, Prodam F, Gauna C, Muccioli G, Papotti M, Abribat T, Van Der Lely AJ, Ghigo E: Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab 2004;89:3062–3065.
17.
Gauna C, Delhanty PJ, Hofland LJ, Janssen JA, Broglio F, Ross RJ, Ghigo E, van der Lely AJ: Ghrelin stimulates, while des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab 2005;90:1055–1060.
18.
Ariyasu H, Takaya K, Iwakura H, Hosoda H, Akamizu T, Arai Y, Kangawa K, Nakao K: Transgenic mice overexpressing des-acyl ghrelin show small phenotype. Endocrinology 2005;146:355–364.
19.
Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, Date Y, Mondal MS, Shimbara T, Kawagoe T, Murakami N, Miyazato M, Kangawa K, Nakazato M: Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology 2006;147:2306–2314.
20.
Levin BE, Routh VH, Kang L, Sanders NM, Dunn-Meynell AA: Neuronal glucosensing: What do we know after 50 years? Diabetes 2004;53:2521–2528.
21.
Burdakov D, Luckman SM, Verkhratsky A: Glucose-sensing neurons of the hypothalamus. Philos Trans R Soc Lond B Biol Sci 2005;360:2227–2235.
22.
Penicaud L, Leloup C, Lorsignol A, Alquier T, Guillod E: Brain glucose sensing mechanism and glucose homeostasis. Curr Opin Clin Nutr Metab Care 2002;5:539–543.
23.
Thorens B: A gene knockout approach in mice to identify glucose sensors controlling glucose homeostasis. Pflügers Arch 2003;445:482–490.
24.
Marty N, Dallaporta M, Foretz M, Emery M, Tarussio D, Bady I, Binnert C, Beermann F, Thorens B: Regulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors. J Clin Invest 2005;115:3545–3553.
25.
Kim MS, Yoon CY, Park KH, Shin CS, Park KS, Kim SY, Cho BY, Lee HK: Changes in ghrelin and ghrelin receptor expression according to feeding status. Neuroreport 2003;14:1317–1320.
26.
Chen X, Ge YL, Jiang ZY, Liu CQ, Depoortere I, Peeters TL: Effects of ghrelin on hypothalamic glucose-responding neurons in rats. Brain Res 2005;1055:131–136.
27.
Cowley MA, Smith RG, Diano S, Tschop M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu H, Pinto S, Colmers WF, Cone RD, Horvath TL: The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 2003;37:649–661.
28.
Chen HY, Trumbauer ME, Chen AS, Weingarth DT, Adams JR, Frazier EG, Shen Z, Marsh DJ, Feighner SD, Guan XM, Ye Z, Nargund RP, Smith RG, Van Der Ploeg LH, Howard AD, MacNeil DJ, Qian S: Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 2004;145:2607–2612.
29.
Bailey ART, Von Englehardt N, Smith RG, Leng G, Dickson SL: Growth hormone secretagogue activation of the arcuate nucleus and brainstem occurs via a non-noradrenergic pathway. J Neuroendocrinol 2000;12:191–198.
30.
Dickson SL, Viltart O, Bailey AR, Leng G: Attenuation of the growth hormone secretagogue induction of fos protein in the rat arcuate nucleus by central somatostatin action. Neuroendocrinology 1997;66:188–194.
31.
Zheng H, Bailey ART, Jiang M-H, Honda K, Chen HY, Trumbauer ME, Van der Ploeg LHT, Schaeffer JM, Leng G, Smith RG: Somatostatin receptor subtype-2 knockout mice are refractory to growth hormone negative feedback on arcuate neurons. Mol Endocrinol 1997;11:1709–1717.
32.
Solomon A, De Fanti BA, Martinez JA: The nucleus tractus solitari participates in peripheral ghrelin glucostatic hunger signalling mediated by insulin. Neuropeptides 2006;40:169–175.
33.
Poykko SM, Kellokoski E, Horkko S, Kauma H, Kesaniemi YA, Ukkola O: Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 2003;52:2546–2553.
34.
Broglio F, Gottero C, Benso A, Prodam F, Volante M, Destefanis S, Gauna C, Muccioli G, Papotti M, van der Lely AJ, Ghigo E: Ghrelin and the endocrine pancreas. Endocrine 2003;22:19–24.
35.
Date Y, Nakazato M, Hashiguchi S, Dezaki K, Mondal MS, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S: Ghrelin is present in pancreatic α cells of humans and rats and stimulates insulin secretion. Diabetes 2002;51:124–129.
36.
Volante M, Allia E, Gugliotta P, Funaro A, Broglio F, Deghenghi R, Muccioli G, Ghigo E, Papotti M: Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab 2002;87:1300–1308.
37.
Wierup N, Yang S, McEvilly RJ, Mulder H, Sundler F: Ghrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells. J Histochem Cytochem 2004;52:301–310.
38.
Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L: Ghrelin cells replace insulin-producing β cells in two mouse models of pancreas development. Proc Natl Acad Sci USA 2004;101:2924–2929.
39.
Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, Van der Ploeg LH, Howard AD: Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res 1997;48:23–29.
40.
Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, 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.
41.
Kageyama H, Funahashi H, Hirayama M, Takenoya F, Kita T, Kato S, Sakurai J, Lee EY, Inoue S, Date Y, Nakazato M, Kangawa K, Shioda S: Morphological analysis of ghrelin and its receptor distribution in the rat pancreas. Regul Pept 2005;126:67–71.
42.
Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS: A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001;50:1714–1719.
43.
Holdstock C, Ludvigsson J, Karlsson FA: Abnormal ghrelin secretion in new onset childhood type 1 diabetes. Diabetologia 2004;47:150–151.
44.
Soriano-Guillen L, Barrios V, Lechuga-Sancho A, Chowen JA, Argente J: Response of circulating ghrelin levels to insulin therapy in children with newly diagnosed type 1 diabetes mellitus. Pediatr Res 2004;55:830–835.
45.
Katsuki A, Urakawa H, Gabazza EC, Murashima S, Nakatani K, Togashi K, Yano Y, Adachi Y, Sumida Y: Circulating levels of active ghrelin is associated with abdominal adiposity, hyperinsulinemia and insulin resistance in patients with type 2 diabetes mellitus. Eur J Endocrinol 2004;151:573–577.
46.
Murdolo G, Lucidi P, Di Loreto C, Parlanti N, De Cicco A, Fatone C, Fanelli CG, Bolli GB, Santeusanio F, De Feo P: Insulin is required for prandial ghrelin suppression in humans. Diabetes 2003;52:2923–2927.
47.
Kahn BB, Flier JS: Obesity and insulin resistance. J Clin Invest 2000;106:473–481.
48.
Booth DA: Some characteristics of feeding during streptoxotocin-induced diabetes in the rat. J Comp Physiol Psychol 1972;80:238–249.
49.
Ishii S, Kamegai J, Tamura H, Shimizu T, Sugihara H, Oikawa S: Role of ghrelin in streptozotocin-induced diabetic hyperphagia. Endocrinology 2002;143:4934–4937.
50.
Dong J, Peeters TL, De Smet B, Moechars D, Delporte C, Vanden Berghe P, Coulie B, Tang M, Depoortere I: Role of endogenous ghrelin in the hyperphagia of mice with streptozotocin-induced diabetes. Endocrinology 2006;147:2634–2642.
51.
Wortley KE, Del Rincon JP, Murray JD, Garcia K, Iida K, Thorner MO, Sleeman MW: Absence of ghrelin protects against early-onset obesity. J Clin Invest 2005;115:3573–3578.
52.
Wortley KE, Anderson KD, Garcia K, Murray JD, Malinova L, Liu R, Moncrieffe M, Thabet K, Cox HJ, Yancopoulos GD, Wiegand SJ, Sleeman MW: Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci USA 2004;101:8227–8232.
53.
Broglio F, Gottero C, Prodam F, Destefanis S, Gauna C, Me E, Riganti F, Vivenza D, Rapa A, Martina V, Arvat E, Bona G, van der Lely AJ, Ghigo E: Ghrelin secretion is inhibited by glucose load and insulin-induced hypoglycaemia but unaffected by glucagon and arginine in humans. Clin Endocrinol (Oxf) 2004;61:503–509.
54.
Lee HM, Wang G, Englander EW, Kojima M, Greeley GH Jr: Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 2002;143:185–190.
55.
Egido EM, Rodriguez-Gallardo J, Silvestre RA, Marco J: Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. Eur J Endocrinol 2002;146:241–244.
56.
Reimer MK, Pacini G, Ahren B: Dose-dependent inhibition by ghrelin of insulin secretion in the mouse. Endocrinology 2003;144:916–921.
57.
Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, van der Lely AJ, Deghenghi R, Ghigo E: Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 2001;86:5083–5086.
58.
Broglio F, Gottero C, Benso A, Prodam F, Destefanis S, Gauna C, Maccario M, Deghenghi R, van der Lely AJ, Ghigo E: Effects of ghrelin on the insulin and glycemic responses to glucose, arginine, or free fatty acids load in humans. J Clin Endocrinol Metab 2003;88:4268–4272.
59.
Bagnasco M, Kalra PS, Kalra SP: Ghrelin and leptin pulse discharge in fed and fasted rats. Endocrinology 2002;143:726–729.
60.
Bagnasco M, Dube MG, Katz A, Kalra PS, Kalra SP: Leptin expression in hypothalamic PVN reverses dietary obesity and hyperinsulinemia but stimulates ghrelin. Obes Res 2003;11:1463–1470.
61.
Seufert J: Leptin effects on pancreatic β-cell gene expression and function. Diabetes 2004;53(suppl 1):S152–S158.
62.
Murata M, Okimura Y, Iida K, Matsumoto M, Sowa H, Kaji H, Kojima M, Kangawa K, Chihara K: Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J Biol Chem 2002;277:5667–5674.
63.
Anderwald C, Muller G, Koca G, Furnsinn C, Waldhausl W, Roden M: Short-term leptin-dependent inhibition of hepatic gluconeogenesis is mediated by insulin receptor substrate-2. Mol Endocrinol 2002;16:1612–1628.
64.
Ceddia RB, Koistinen HA, Zierath JR, Sweeney G: Analysis of paradoxical observations on the association between leptin and insulin resistance. FASEB J 2002;16:1163–1176.
65.
Sun Y, Asnicar M, Saha PK, Chan L, Smith RG: Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice. Cell Metab 2006;3:379–386.
66.
Dezaki K, Hosoda H, Kakei M, Hashiguchi S, Watanabe M, Kangawa K, Yada T: Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in β cells: implication in the glycemic control in rodents. Diabetes 2004;53:3142–3151.
67.
Gauna C, Meyler FM, Janssen JA, Delhanty PJ, Abribat T, van Koetsveld P, Hofland LJ, Broglio F, Ghigo E, van der Lely AJ: 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.
68.
Ariyasu H, Takaya K, Hosoda H, Iwakura H, Ebihara K, Mori K, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K: Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by a specific RIA for the active form of ghrelin. Endocrinology 2002;143:3341–3350.
69.
Asakawa A, Inui A, Kaga T, Katsuura G, Fujimiya M, Fujino MA, Kasuga M: Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003;52:947–952.
70.
Poitout V, Robertson RP: An integrated view of β-cell dysfunction in type 2 diabetes. Annu Rev Med 1996;47:69–83.
71.
Zhang CY, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, Hagen T, Vidal-Puig AJ, Boss O, Kim YB, Zheng XX, Wheeler MB, Shulman GI, Chan CB, Lowell BB: Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, β-cell dysfunction, and type 2 diabetes. Cell 2001;105:745–755.
72.
Erlanson-Albertsson C: The role of uncoupling proteins in the regulation of metabolism. Acta Physiol Scand 2003;178:405–412.
73.
Blander G, Guarente L: The Sir2 family of protein deacetylases. Annu Rev Biochem 2004;73:417–435.
74.
Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J, McDonagh T, Lemieux M, McBurney M, Szilvasi A, Easlon EJ, Lin SJ, Guarente L: Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic β cells. PLoS Biol 2006;4:e31.
75.
Moynihan KA, Grimm AA, Plueger MM, Bernal-Mizrachi E, Ford E, Cras-Meneur C, Permutt MA, Imai S: Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice. Cell Metab 2005;2:105–117.
76.
Doi A, Shono T, Nishi M, Furuta H, Sasaki H, Nanjo K: IA-2β, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion. Proc Natl Acad Sci USA 2006;103:885–890.
77.
Fagan SP, Azizzadeh A, Moldovan S, Ray MK, Adrian TE, Ding X, Coy DH, Brunicardi FC: Insulin secretion is inhibited by subtype five somatostatin receptor in the mouse. Surgery 1998;124:254–259.
78.
Tirone TA, Norman MA, Moldovan S, DeMayo FJ, Wang XP, Brunicardi FC: Pancreatic somatostatin inhibits insulin secretion via SSTR-5 in the isolated perfused mouse pancreas model. Pancreas 2003;26:e67–e73.
79.
Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K: Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol 2001;280:R1483–R1487.
80.
Nagaya N, Miyatake K, Uematsu M, Oya H, Shimizu W, Hosoda H, Kojima M, Nakanishi N, Mori H, Kangawa K: Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab 2001;86:5854–5859.
81.
Nonogaki K, Ohashi-Nozue K, Oka Y: A negative feedback system between brain serotonin systems and plasma active ghrelin levels in mice. Biochem Biophys Res Commun 2006;341:703–707.
82.
Adeghate E, Ponery AS, Pallot D, Parvez SH, Singh J: Distribution of serotonin and its effect on insulin and glucagon secretion in normal and diabetic pancreatic tissues in rat. Neuroendocrinol Lett 1999;20:315–322.
83.
Iwakura H, Hosoda K, Son C, Fujikura J, Tomita T, Noguchi M, Ariyasu H, Takaya K, Masuzaki H, Ogawa Y, Hayashi T, Inoue G, Akamizu T, Hosoda H, Kojima M, Itoh H, Toyokuni S, Kangawa K, Nakao K: Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice. J Biol Chem 2005;280:15247–15256.
84.
Granata R, Settanni F, Catapano F, Trovato L, Destefanis S, Gallo D, Isgaard J, Muccioli G, Ghigo E: [p2–166] acylated and unacylated ghrelin promote proliferation and inhibit serum starvation- and cytokine-induced apoptosis of pancreatic β cells through camp/pka, erk1/2 and pi3k/akt: ENDO 2006. Boston/Mass, The Endocrine Society, 2006.
85.
Toshinai K, Date Y, Murakami N, Shimada M, Mondal MS, Shimbara T, Guan JL, Wang QP, Funahashi H, Sakurai T, Shioda S, Matsukura S, Kangawa K, Nakazato M: Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology 2003;144:1506– 1512.
86.
Cai XJ, Widdowson PS, Harrold J, Wilson S, Buckingham RE, Arch JR, Tadayyon M, Clapham JC, Wilding J, Williams G: Hypothalamic orexin expression: modulation by blood glucose and feeding. Diabetes 1999;48:2132–2137.
87.
Nowak KW, Mackowiak P, Switonska MM, Fabis M, Malendowicz LK: Acute orexin effects on insulin secretion in the rat: In vivo and in vitro studies. Life Sci 2000;66:449–454.
88.
Nakabayashi M, Suzuki T, Takahashi K, Totsune K, Muramatsu Y, Kaneko C, Date F, Takeyama J, Darnel AD, Moriya T, Sasano H: Orexin-A expression in human peripheral tissues. Mol Cell Endocrinol 2003;205:43–50.
89.
Ouedraogo R, Naslund E, Kirchgessner AL: Glucose regulates the release of orexin-A from the endocrine pancreas. Diabetes 2003;52:111–117.
90.
Kirchgessner AL: Orexins in the brain-gut axis. Endocr Rev 2002;23:1–15.
91.
Gauna C, Delhanty PJ, van Aken MO, Janssen JA, Themmen AP, Hofland LJ, Culler M, Broglio F, Ghigo E, van der Lely AJ: 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. Mol Cell Endocrinol 2006;251:103–111.
92.
Depoortere I, Thijs T, Peeters T: The contractile effect of the ghrelin receptor antagonist, D-Lys3-GHRP-6, in rat fundic strips is mediated through 5-HT receptors. Eur J Pharmacol 2006;537:160–165.
93.
Ohkura M, Tanaka N, Kobayashi H, Wada A, Nakai J, Yamamoto R: Insulin induces internalization of the 5-HT2a receptor expressed in HEK293 cells. Eur J Pharmacol 2005;518:18–21.
94.
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.
95.
Ahima RS: Ghrelin - A new player in glucose homeostasis? Cell Metab 2006;3:301–302.
© 2007 S. Karger AG, Basel
2007
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.