Journal of Molecular Endocrinology

References

1. ↵
   1. Ackermann AM &
   2. Gannon M

   2007 Molecular regulation of pancreatic beta-cell mass development, maintenance, and expansion. Journal of Molecular Endocrinology 38 193–206.doi:10.1677/JME-06-0053.
2. ↵
   1. Adeghate E &
   2. Ponery AS

   2002 Ghrelin stimulates insulin secretion from the pancreas of normal and diabetic rats. Journal of Neuroendocrinology 14 555–560.doi:10.1046/j.1365-2826.2002.00811.x.
3. ↵
   1. Andralojc KM,
   2. Mercalli A,
   3. Nowak KW,
   4. Albarello L,
   5. Calcagno R,
   6. Luzi L,
   7. Bonifacio E,
   8. Doglioni C &
   9. Piemonti L

   2009 Ghrelin-producing epsilon cells in the developing and adult human pancreas. Diabetologia 52 486–493.doi:10.1007/s00125-008-1238-y.
4. ↵
   1. Assmann A,
   2. Hinault C &
   3. Kulkarni RN

   2009 Growth factor control of pancreatic islet regeneration and function. Pediatric Diabetes 10 14–32.doi:10.1111/j.1399-5448.2008.00468.x.
5. ↵
   1. Bonal C &
   2. Herrera PL

   2008 Genes controlling pancreas ontogeny. International Journal of Developmental Biology 52 823–835.doi:10.1387/ijdb.072444cb.
6. ↵
   1. Ceranowicz P,
   2. Warzecha Z,
   3. Dembinski A,
   4. Cieszkowski J,
   5. Dembinski M,
   6. Sendur R,
   7. Kusnierz-Cabala B,
   8. Tomaszewska R,
   9. Kuwahara A &
   10. Kato I

   2009 Pretreatment with obestatin inhibits the development of cerulein-induced pancreatitis. Journal of Physiology and Pharmacology 60 95–101.
7. ↵
   1. Chanoine JP &
   2. Wong AC

   2004 Ghrelin gene expression is markedly higher in fetal pancreas compared with fetal stomach: effect of maternal fasting. Endocrinology 145 3813–3820.doi:10.1210/en.2004-0053.
8. ↵
   1. Chanoine JP,
   2. Wong AC &
   3. Barrios V

   2006 Obestatin, acylated and total ghrelin concentrations in the perinatal rat pancreas. Hormone Research 66 81–88.doi:10.1159/000093585.
9. ↵
   1. Chanoine JP,
   2. De Waele K &
   3. Walia P

   Ghrelin and the growth hormone secretagogue receptor in growth and developmentInternational Journal of Obesity 33 Supplement 1 2009 S48–S52.doi:10.1038/ijo.2009.17.
10. ↵
    1. Chao CS,
    2. Loomis ZL,
    3. Lee JE &
    4. Sussel L

    2007 Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells. Developmental Biology 312 523–532.doi:10.1016/j.ydbio.2007.09.057.
11. ↵
    1. Cheng H,
    2. Straub SG &
    3. Sharp GW

    2007 Inhibitory role of Src family tyrosine kinases on Ca²⁺-dependent insulin release. American Journal of Physiology. Endocrinology and Metabolism 292 E845–E852.doi:10.1152/ajpendo.00103.2006.
12. ↵
    1. Colombo M,
    2. Gregersen S,
    3. Xiao J &
    4. Hermansen K

    2003 Effects of ghrelin and other neuropeptides (CART, MCH, orexin A and B, and GLP-1) on the release of insulin from isolated rat islets. Pancreas 27 161–166.doi:10.1097/00006676-200308000-00009.
13. ↵
    1. Costes S,
    2. Broca C,
    3. Bertrand G,
    4. Lajoix AD,
    5. Bataille D,
    6. Bockaert J &
    7. Dalle S

    2006 ERK1/2 control phosphorylation and protein level of cAMP-responsive element-binding protein: a key role in glucose-mediated pancreatic beta-cell survival. Diabetes 55 2220–2230.doi:10.2337/db05-1618.
14. ↵
    1. Date Y,
    2. Nakazato M,
    3. Hashiguchi S,
    4. Dezaki K,
    5. Mondal MS,
    6. Hosoda H,
    7. Kojima M,
    8. Kangawa K,
    9. Arima T,
    10. Matsuo H
    11. et al.

    2002 Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. Diabetes 51 124–129.doi:10.2337/diabetes.51.1.124.
15. ↵
    1. Dezaki K,
    2. Hosoda H,
    3. Kakei M,
    4. Hashiguchi S,
    5. Watanabe M,
    6. Kangawa K &
    7. Yada T

    2004 Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca²⁺ signaling in beta-cells: implication in the glycemic control in rodents. Diabetes 53 3142–3151.doi:10.2337/diabetes.53.12.3142.
16. ↵
    1. Dezaki K,
    2. Sone H,
    3. Koizumi M,
    4. Nakata M,
    5. Kakei M,
    6. Nagai H,
    7. Hosoda H,
    8. Kangawa K &
    9. Yada T

    2006 Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance. Diabetes 55 3486–3493.doi:10.2337/db06-0878.
17. ↵
    1. Dezaki K,
    2. Kakei M &
    3. Yada T

    2007 Ghrelin uses Gα_i2 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 56 2319–2327.doi:10.2337/db07-0345.
18. ↵
    1. Dezaki K,
    2. Sone H &
    3. Yada T

    2008 Ghrelin is a physiological regulator of insulin release in pancreatic islets and glucose homeostasis. Pharmacology and Therapeutics 118 239–249.doi:10.1016/j.pharmthera.2008.02.008.
19. ↵
    1. Doi A,
    2. Shono T,
    3. Nishi M,
    4. Furuta H,
    5. Sasaki H &
    6. Nanjo K

    2006 IA-2beta, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion. PNAS 103 885–890.doi:10.1073/pnas.0502470102.
20. ↵
    1. Dong XY,
    2. He JM,
    3. Tang SQ,
    4. Li HY,
    5. Jiang QY &
    6. Zou XT

    2009 Is GPR39 the natural receptor of obestatin? Peptides 30 431–438.doi:10.1016/j.peptides.2008.09.022.
21. ↵
    1. Drucker DJ

    2006 The biology of incretin hormones. Cell Metabolism 3 153–165.doi:10.1016/j.cmet.2006.01.004.
22. ↵
    1. Egido EM,
    2. Rodriguez-Gallardo J,
    3. Silvestre RA &
    4. Marco J

    2002 Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. European Journal of Endocrinology 146 241–244.doi:10.1530/eje.0.1460241.
23. ↵
    1. Egido EM,
    2. Hernandez R,
    3. Marco J &
    4. Silvestre RA

    2008 Effect of obestatin on insulin, glucagon and somatostatin secretion in the perfused rat pancreas. Regulatory Peptides 152 61–66.doi:10.1016/j.regpep.2008.08.003.
24. ↵
    1. Filigheddu N,
    2. Gnocchi VF,
    3. Coscia M,
    4. Cappelli M,
    5. Porporato PE,
    6. Taulli R,
    7. Traini S,
    8. Baldanzi G,
    9. Chianale F,
    10. Cutrupi S
    11. et al.

    2007 Ghrelin and des-acyl ghrelin promote differentiation and fusion of C2C12 skeletal muscle cells. Molecular Biology of the Cell 18 986–994.doi:10.1091/mbc.E06-05-0402.
25. ↵
    1. Gauna C,
    2. Delhanty PJ,
    3. van Aken MO,
    4. Janssen JA,
    5. Themmen AP,
    6. Hofland LJ,
    7. Culler M,
    8. Broglio F,
    9. Ghigo E &
    10. van der Lely AJ

    2006 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 251 103–111.doi:10.1016/j.mce.2006.03.040.
26. ↵
    1. Gnanapavan S,
    2. Kola B,
    3. Bustin SA,
    4. Morris DG,
    5. McGee P,
    6. Fairclough P,
    7. Bhattacharya S,
    8. Carpenter R,
    9. Grossman AB &
    10. Korbonits M

    2002 The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. Journal of Clinical Endocrinology and Metabolism 87 2988doi:10.1210/jc.87.6.2988.
27. ↵
    1. Gourcerol G &
    2. Tache Y

    2007 Obestatin – a ghrelin-associated peptide that does not hold its promise to suppress food intake and motility. Neurogastroenterology and Motility 19 161–165.doi:10.1111/j.1365-2982.2007.00916.x.
28. ↵
    1. Granata R,
    2. Settanni F,
    3. Trovato L,
    4. Destefanis S,
    5. Gallo D,
    6. Martinetti M,
    7. Ghigo E &
    8. Muccioli G

    2006 Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HIT-T15 pancreatic beta-cells. Journal of Endocrinological Investigation 29 RC19–RC22.
29. ↵
    1. Granata R,
    2. Settanni F,
    3. Biancone L,
    4. Trovato L,
    5. Nano R,
    6. Bertuzzi F,
    7. Destefanis S,
    8. Annunziata M,
    9. Martinetti M,
    10. Catapano F
    11. et al.

    2007 Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3′,5′-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-kinase/Akt signaling. Endocrinology 148 512–529.doi:10.1210/en.2006-0266.
30. ↵
    1. Granata R,
    2. Settanni F,
    3. Gallo D,
    4. Trovato L,
    5. Biancone L,
    6. Cantaluppi V,
    7. Nano R,
    8. Annunziata M,
    9. Campiglia P,
    10. Arnoletti E
    11. et al.

    2008 Obestatin promotes survival of pancreatic beta-cells and human islets and induces expression of genes involved in the regulation of beta-cell mass and function. Diabetes 57 967–979.doi:10.2337/db07-1104.
31. ↵
    1. Granata R,
    2. Volante M,
    3. Settanni F,
    4. Gauna C,
    5. Ghé C,
    6. Annunziata M,
    7. Deidda B,
    8. Gesmundo I,
    9. Abribat T,
    10. van der Lely AJ
    11. et al.

    2010 Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats. Journal of Molecular Endocrinology 45 9–17.doi:10.1677/JME-09-0141.
32. ↵
    1. Gronberg M,
    2. Tsolakis AV,
    3. Magnusson L,
    4. Janson ET &
    5. Saras J

    2008 Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands. Journal of Histochemistry and Cytochemistry 56 793–801.doi:10.1369/jhc.2008.951145.
33. ↵
    1. Gutierrez JA,
    2. Solenberg PJ,
    3. Perkins DR,
    4. Willency JA,
    5. Knierman MD,
    6. Jin Z,
    7. Witcher DR,
    8. Luo S,
    9. Onyia JE &
    10. Hale JE

    2008 Ghrelin octanoylation mediated by an orphan lipid transferase. PNAS 105 6320–6325.doi:10.1073/pnas.0800708105.
34. ↵
    1. Heller RS,
    2. Jenny M,
    3. Collombat P,
    4. Mansouri A,
    5. Tomasetto C,
    6. Madsen OD,
    7. Mellitzer G,
    8. Gradwohl G &
    9. Serup P

    2005 Genetic determinants of pancreatic epsilon-cell development. Developmental Biology 286 217–224.doi:10.1016/j.ydbio.2005.06.041.
35. ↵
    1. Hill JT,
    2. Mastracci TL,
    3. Vinton C,
    4. Doyle ML,
    5. Anderson KR,
    6. Loomis ZL,
    7. Schrunk JM,
    8. Minic AD,
    9. Prabakar KR,
    10. Pugliese A
    11. et al.

    2009 Ghrelin is dispensable for embryonic pancreatic islet development and differentiation. Regulatory Peptides 157 51–56.doi:10.1016/j.regpep.2009.02.013.
36. ↵
    1. Hill JT,
    2. Chao CS,
    3. Anderson KR,
    4. Kaufman F,
    5. Johnson CW &
    6. Sussel L

    2010 Nkx2.2 activates the ghrelin promoter in pancreatic islet cells. Molecular Endocrinology 24 381–390.doi:10.1210/me.2009-0360.
37. ↵
    1. Holst B,
    2. Egerod KL,
    3. Schild E,
    4. Vickers SP,
    5. Cheetham S,
    6. Gerlach LO,
    7. Storjohann L,
    8. Stidsen CE,
    9. Jones R,
    10. Beck-Sickinger AG
    11. et al.

    2007 GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology 148 13–20.doi:10.1210/en.2006-0933.
38. ↵
    1. Holst B,
    2. Egerod KL,
    3. Jin C,
    4. Petersen PS,
    5. Ostergaard MV,
    6. Hald J,
    7. Sprinkel AM,
    8. Storling J,
    9. Mandrup-Poulsen T,
    10. Holst JJ
    11. et al.

    2009 G protein-coupled receptor 39 deficiency is associated with pancreatic islet dysfunction. Endocrinology 150 2577–2585.doi:10.1210/en.2008-1250.
39. ↵
    1. Howard AD,
    2. Feighner SD,
    3. Cully DF,
    4. Arena JP,
    5. Liberator PA,
    6. Rosenblum CI,
    7. Hamelin M,
    8. Hreniuk DL,
    9. Palyha OC,
    10. Anderson J
    11. et al.

    1996 A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273 974–977.doi:10.1126/science.273.5277.974.
40. ↵
    1. Inhoff T,
    2. Wiedenmann B,
    3. Klapp BF,
    4. Monnikes H &
    5. Kobelt P

    2009 Is desacyl ghrelin a modulator of food intake? Peptides 30 991–994.doi:10.1016/j.peptides.2009.01.019.
41. ↵
    1. Irako T,
    2. Akamizu T,
    3. Hosoda H,
    4. Iwakura H,
    5. Ariyasu H,
    6. Tojo K,
    7. Tajima N &
    8. Kangawa K

    2006 Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats. Diabetologia 49 1264–1273.doi:10.1007/s00125-006-0226-3.
42. ↵
    1. Iwakura H,
    2. Hosoda K,
    3. Son C,
    4. Fujikura J,
    5. Tomita T,
    6. Noguchi M,
    7. Ariyasu H,
    8. Takaya K,
    9. Masuzaki H,
    10. Ogawa Y
    11. et al.

    2005 Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice. Journal of Biological Chemistry 280 15247–15256.doi:10.1074/jbc.M411358200.
43. ↵
    1. Jhala US,
    2. Canettieri G,
    3. Screaton RA,
    4. Kulkarni RN,
    5. Krajewski S,
    6. Reed J,
    7. Walker J,
    8. Lin X,
    9. White M &
    10. Montminy M

    2003 cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes and Development 17 1575–1580.doi:10.1101/gad.1097103.
44. ↵
    1. Kageyama H,
    2. Funahashi H,
    3. Hirayama M,
    4. Takenoya F,
    5. Kita T,
    6. Kato S,
    7. Sakurai J,
    8. Lee EY,
    9. Inoue S,
    10. Date Y
    11. et al.

    2005 Morphological analysis of ghrelin and its receptor distribution in the rat pancreas. Regulatory Peptides 126 67–71.doi:10.1016/j.regpep.2004.08.031.
45. ↵
    1. Kerem M,
    2. Salman B,
    3. Ozsoy S,
    4. Pasaoglu H,
    5. Bedirli A,
    6. Haziroglu R &
    7. Yilmaz TU

    2009 Exogenous ghrelin enhances endocrine and exocrine regeneration in pancreatectomized rats. Journal of Gastrointestinal Surgery 13 775–783.doi:10.1007/s11605-008-0778-2.
46. ↵
    1. Kim SW,
    2. Her SJ,
    3. Park SJ,
    4. Kim D,
    5. Park KS,
    6. Lee HK,
    7. Han BH,
    8. Kim MS,
    9. Shin CS &
    10. Kim SY

    2005 Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells. Bone 37 359–369.doi:10.1016/j.bone.2005.04.020.
47. ↵
    1. Kojima M,
    2. Hosoda H,
    3. Date Y,
    4. Nakazato M,
    5. Matsuo H &
    6. Kangawa K

    1999 Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402 656–660.doi:10.1038/45230.
48. ↵
    1. van der Lely AJ

    Ghrelin and new metabolic frontiersHormone Research 71 Supplement 1 2009 129–133.doi:10.1159/000178055.
49. ↵
    1. van der Lely AJ,
    2. Tschop M,
    3. Heiman ML &
    4. Ghigo E

    2004 Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocrine Reviews 25 426–457.doi:10.1210/er.2002-0029.
50. ↵
    1. Mandrup-Poulsen T

    β-Cell apoptosis: stimuli and signalingDiabetes 50 Supplement 1 2001 S58–S63.doi:10.2337/diabetes.50.2007.S58.
51. ↵
    1. McCabe C,
    2. Samali A &
    3. O'Brien T

    2006 β-Cell cytoprotective strategies: establishing the relative roles for iNOS and ROS. Biochemical and Biophysical Research Communications 342 1240–1248.doi:10.1016/j.bbrc.2006.02.092.
52. ↵
    1. Montrose-Rafizadeh C,
    2. Avdonin P,
    3. Garant MJ,
    4. Rodgers BD,
    5. Kole S,
    6. Yang H,
    7. Levine MA,
    8. Schwindinger W &
    9. Bernier M

    1999 Pancreatic glucagon-like peptide-1 receptor couples to multiple G proteins and activates mitogen-activated protein kinase pathways in Chinese hamster ovary cells. Endocrinology 140 1132–1140.doi:10.1210/en.140.3.1132.
53. ↵
    1. Muccioli G,
    2. Baragli A,
    3. Granata R,
    4. Papotti M &
    5. Ghigo E

    2007 Heterogeneity of ghrelin/growth hormone secretagogue receptors. Toward the understanding of the molecular identity of novel ghrelin/GHS receptors. Neuroendocrinology 86 147–164.doi:10.1159/000105141.
54. ↵
    1. Oliver-Krasinski JM,
    2. Kasner MT,
    3. Yang J,
    4. Crutchlow MF,
    5. Rustgi AK,
    6. Kaestner KH &
    7. Stoffers DA

    2009 The diabetes gene Pdx1 regulates the transcriptional network of pancreatic endocrine progenitor cells in mice. Journal of Clinical Investigation 119 1888–1898.doi:10.1172/JCI37028.
55. ↵
    1. Park S,
    2. Dong X,
    3. Fisher TL,
    4. Dunn S,
    5. Omer AK,
    6. Weir G &
    7. White MF

    2006 Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function. Journal of Biological Chemistry 281 1159–1168.doi:10.1074/jbc.M508307200.
56. ↵
    1. Pazos Y,
    2. Alvarez CJ,
    3. Camina JP,
    4. Al-Massadi O,
    5. Seoane LM &
    6. Casanueva FF

    2009 Role of obestatin on growth hormone secretion: an in vitro approach. Biochemical and Biophysical Research Communications 390 1377–1381.doi:10.1016/j.bbrc.2009.10.163.
57. ↵
    1. Prado CL,
    2. Pugh-Bernard AE,
    3. Elghazi L,
    4. Sosa-Pineda B &
    5. Sussel L

    2004 Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. PNAS 101 2924–2929.doi:10.1073/pnas.0308604100.
58. ↵
    1. Qader SS,
    2. Lundquist I,
    3. Ekelund M,
    4. Hakanson R &
    5. Salehi A

    2005 Ghrelin activates neuronal constitutive nitric oxide synthase in pancreatic islet cells while inhibiting insulin release and stimulating glucagon release. Regulatory Peptides 128 51–56.doi:10.1016/j.regpep.2004.12.018.
59. ↵
    1. Qader SS,
    2. Hakanson R,
    3. Rehfeld JF,
    4. Lundquist I &
    5. Salehi A

    2008 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 146 230–237.doi:10.1016/j.regpep.2007.09.017.
60. ↵
    1. Ragvin A,
    2. Moro E,
    3. Fredman D,
    4. Navratilova P,
    5. Drivenes Ø,
    6. Engström PG,
    7. Alonso ME,
    8. Mustienes Ede L,
    9. Skarmeta JL,
    10. Tavares MJ
    11. et al.

    2010 Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3. PNAS 107 775–780.doi:10.1073/pnas.0911591107.
61. ↵
    1. Reimer MK,
    2. Pacini G &
    3. Ahren B

    2003 Dose-dependent inhibition by ghrelin of insulin secretion in the mouse. Endocrinology 144 916–921.doi:10.1210/en.2002-220819.
62. ↵
    1. Ren AJ,
    2. Guo ZF,
    3. Wang YK,
    4. Lin L,
    5. Zheng X &
    6. Yuan WJ

    2008a Obestatin, obesity and diabetes. Peptides 30 439–444.doi:10.1016/j.peptides.2008.10.002.
63. ↵
    1. Ren AJ,
    2. Guo ZF,
    3. Wang YK,
    4. Wang LG,
    5. Wang WZ,
    6. Lin L,
    7. Zheng X &
    8. Yuan WJ

    2008b Inhibitory effect of obestatin on glucose-induced insulin secretion in rats. Biochemical and Biophysical Research Communications 369 969–972.doi:10.1016/j.bbrc.2008.02.146.
64. ↵
    1. Salehi A,
    2. Dornonville de la Cour C,
    3. Hakanson R &
    4. Lundquist I

    2004 Effects of ghrelin on insulin and glucagon secretion: a study of isolated pancreatic islets and intact mice. Regulatory Peptides 118 143–150.doi:10.1016/j.regpep.2003.12.001.
65. ↵
    1. Samson SL &
    2. Chan L

    2006 Gene therapy for diabetes: reinventing the islet. Trends in Endocrinology and Metabolism 17 92–100.doi:10.1016/j.tem.2006.02.002.
66. ↵
    1. Soares JB &
    2. Leite-Moreira AF

    2008 Ghrelin, des-acyl ghrelin and obestatin: three pieces of the same puzzle. Peptides 29 1255–1270.doi:10.1016/j.peptides.2008.02.018.
67. ↵
    1. Soyer J,
    2. Flasse L,
    3. Raffelsberger W,
    4. Beucher A,
    5. Orvain C,
    6. Peers B,
    7. Ravassard P,
    8. Vermot J,
    9. Voz ML,
    10. Mellitzer G
    11. et al.

    2010 Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development. Development 137 203–212.doi:10.1242/dev.041673.
68. ↵
    1. Sun Y,
    2. Wang P,
    3. Zheng H &
    4. Smith RG

    2004 Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. PNAS 101 4679–4684.doi:10.1073/pnas.0305930101.
69. ↵
    1. Sun Y,
    2. Asnicar M &
    3. Smith RG

    2007 Central and peripheral roles of ghrelin on glucose homeostasis. Neuroendocrinology 86 215–228.doi:10.1159/000109094.
70. ↵
    1. Tang SQ,
    2. Jiang QY,
    3. Zhang YL,
    4. Zhu XT,
    5. Shu G,
    6. Gao P,
    7. Feng DY,
    8. Wang XQ &
    9. Dong XY

    2008 Obestatin: its physicochemical characteristics and physiological functions. Peptides 29 639–645.doi:10.1016/j.peptides.2008.01.012.
71. ↵
    1. Terauchi Y,
    2. Takamoto I,
    3. Kubota N,
    4. Matsui J,
    5. Suzuki R,
    6. Komeda K,
    7. Hara A,
    8. Toyoda Y,
    9. Miwa I,
    10. Aizawa S
    11. et al.

    2007 Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in response to high-fat diet-induced insulin resistance. Journal of Clinical Investigation 117 246–257.doi:10.1172/JCI17645.
72. ↵
    1. Tremblay F,
    2. Richard AM,
    3. Will S,
    4. Syed J,
    5. Stedman N,
    6. Perreault M &
    7. Gimeno RE

    2009 Disruption of G protein-coupled receptor 39 impairs insulin secretion in vivo. Endocrinology 150 2586–2595.doi:10.1210/en.2008-1251.
73. ↵
    1. Ueberberg B,
    2. Unger N,
    3. Saeger W,
    4. Mann K &
    5. Petersenn S

    2009 Expression of ghrelin and its receptor in human tissues. Hormone and Metabolic Research 41 814–821.doi:10.1055/s-0029-1233462.
74. ↵
    1. Unniappan S,
    2. Speck M &
    3. Kieffer TJ

    2008 Metabolic effects of chronic obestatin infusion in rats. Peptides 29 1354–1361.doi:10.1016/j.peptides.2008.03.023.
75. ↵
    1. Volante M,
    2. Allia E,
    3. Gugliotta P,
    4. Funaro A,
    5. Broglio F,
    6. Deghenghi R,
    7. Muccioli G,
    8. Ghigo E &
    9. Papotti M

    2002 Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. Journal of Clinical Endocrinology and Metabolism 87 1300–1308.doi:10.1210/jc.87.3.1300.
76. ↵
    1. Volante M,
    2. Rosas R,
    3. Ceppi P,
    4. Rapa I,
    5. Cassoni P,
    6. Wiedenmann B,
    7. Settanni F,
    8. Granata R &
    9. Papotti M

    2009 Obestatin in human neuroendocrine tissues and tumours: expression and effect on tumour growth. Journal of Pathology 218 458–466.doi:10.1002/path.2551.
77. ↵
    1. Walia P,
    2. Asadi A,
    3. Kieffer TJ,
    4. Johnson JD &
    5. Chanoine JP

    2009 Ontogeny of ghrelin, obestatin, preproghrelin, and prohormone convertases in rat pancreas and stomach. Pediatric Research 65 39–44.doi:10.1203/PDR.0b013e31818bc134.
78. ↵
    1. Wang Q,
    2. Elghazi L,
    3. Martin S,
    4. Martins I,
    5. Srinivasan RS,
    6. Geng X,
    7. Sleeman M,
    8. Collombat P,
    9. Houghton J &
    10. Sosa-Pineda B

    2008 Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum. Developmental Dynamics 237 51–61.doi:10.1002/dvdy.21379.
79. ↵
    1. Wang W,
    2. Liu Y,
    3. Chen Y,
    4. Cao C,
    5. Xiang Y,
    6. Zhang D,
    7. Han L,
    8. Zhao H &
    9. Liu G

    2010a Inhibition of Foxo1 mediates protective effects of ghrelin against lipotoxicity in MIN6 pancreatic beta-cells. Peptides 31 307–314.doi:10.1016/j.peptides.2009.11.011.
80. ↵
    1. Wang W,
    2. Zhang D,
    3. Zhao H,
    4. Chen Y,
    5. Liu Y,
    6. Cao C,
    7. Han L &
    8. Liu G

    2010b Ghrelin inhibits cell apoptosis induced by lipotoxicity in pancreatic beta-cell line. Regulatory Peptides 161 43–50.doi:10.1016/j.regpep.2009.12.017.
81. ↵
    1. Wierup N &
    2. Sundler F

    2005 Ultrastructure of islet ghrelin cells in the human fetus. Cell and Tissue Research 319 423–428.doi:10.1007/s00441-004-1044-x.
82. ↵
    1. Wierup N,
    2. Svensson H,
    3. Mulder H &
    4. Sundler F

    2002 The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regulatory Peptides 107 63–69.doi:10.1016/S0167-0115(02)00067-8.
83. ↵
    1. Wierup N,
    2. Yang S,
    3. McEvilly RJ,
    4. Mulder H &
    5. Sundler F

    2004 Ghrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells. Journal of Histochemistry and Cytochemistry 52 301–310.
84. ↵
    1. Yamamoto H,
    2. Uchigata Y &
    3. Okamoto H

    1981 Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets. Nature 294 284–286.doi:10.1038/294284a0.
85. ↵
    1. Yang J,
    2. Brown MS,
    3. Liang G,
    4. Grishin NV &
    5. Goldstein JL

    2008 Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 132 387–396.doi:10.1016/j.cell.2008.01.017.
86. ↵
    1. Zhang JV,
    2. Ren PG,
    3. Avsian-Kretchmer O,
    4. Luo CW,
    5. Rauch R,
    6. Klein C &
    7. Hsueh AJ

    2005 Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science 310 996–999.doi:10.1126/science.1117255.
87. ↵
    1. Zhang Y,
    2. Ying B,
    3. Shi L,
    4. Fan H,
    5. Yang D,
    6. Xu D,
    7. Wei Y,
    8. Hu X,
    9. Zhang Y,
    10. Zhang X
    11. et al.

    2007 Ghrelin inhibit cell apoptosis in pancreatic beta cell line HIT-T15 via mitogen-activated protein kinase/phosphoinositide 3-kinase pathways. Toxicology 237 194–202.doi:10.1016/j.tox.2007.05.013.
88. ↵
    1. Zhang JV,
    2. Jahr H,
    3. Luo CW,
    4. Klein C,
    5. Van Kolen K,
    6. Ver Donck L,
    7. De A,
    8. Baart E,
    9. Li J,
    10. Moechars D
    11. et al.

    2008 Obestatin induction of early-response gene expression in gastrointestinal and adipose tissues and the mediatory role of G protein-coupled receptor, GPR39. Molecular Endocrinology 22 1464–1475.doi:10.1210/me.2007-0569.
89. ↵
    1. Zhao CM,
    2. Furnes MW,
    3. Stenstrom B,
    4. Kulseng B &
    5. Chen D

    2008 Characterization of obestatin- and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: an immunohistochemical and electron-microscopic study. Cell and Tissue Research 331 575–587.doi:10.1007/s00441-007-0514-3.