Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice

American Journal of Physiology - Endocrinology and Metabolism

Volumn 303, Issue 3, 2012, Pages

  Ma, Xiaojun ^a,b   Lin, Yuezhen ^a   Lin, Ligen ^a   Qin, Guijun ^b   Pereira, Fred A ^a   Haymond, Morey W ^a   Butte, Nancy F ^a   Sun, Yuxiang ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIVERSITY   (China)

Author keywords

Growth hormone secretagogue receptor; Insulin secretion; Type 2 diabetes

Indexed keywords

FIBROBLAST GROWTH FACTOR 21; GHRELIN; GHRELIN RECEPTOR; GROWTH HORMONE SECRETAGOGUE RECEPTOR; HORMONE RECEPTOR AFFECTING AGENT; INSULIN; LEPTIN; PROLYLLEUCYLGLYCINAMIDE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TRANSCRIPTION FACTOR PDX 1; UNCOUPLING PROTEIN 2; GLUCOSE;

ABLATION THERAPY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL SIZE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE; HYPERGLYCEMIA; HYPERPHAGIA; INSULIN RELEASE; INSULIN RESISTANCE; MOUSE; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; PANCREAS ISLET CELL FUNCTION; PRIORITY JOURNAL; PROTEIN DEFICIENCY; UPREGULATION; ANIMAL; C57BL MOUSE; COMPARATIVE STUDY; GENE DELETION; GENETICS; GLUCOSE TOLERANCE TEST; HOMEOSTASIS; MALE; METABOLISM; METABOLOME; MOUSE MUTANT; PHYSIOLOGY;

ANIMALS; GENE DELETION; GHRELIN; GLUCOSE; GLUCOSE TOLERANCE TEST; HOMEOSTASIS; HYPERGLYCEMIA; LEPTIN; MALE; METABOLOME; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, OBESE; OBESITY; RECEPTORS, GHRELIN;

EID: 84864514808     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00576.2011     Document Type: Article

References (60)

1. Ahima RS. Antagonism of ghrelin for glycemic control in type 2 diabetes mellitus? Endocrinology 148: 5173-5174, 2007.
2. 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 52: 947-952, 2003.
3. Bresciani E, Rapetti D, Dona F, Bulgarelli I, Tamiazzo L, Locatelli V, Torsello A. Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat. J Endocrinol Invest 29: RC16-RC18, 2006.
4. Briggs DI, Andrews ZB. A recent update on the role of ghrelin in glucose homeostasis. Curr Diabetes Rev 7: 201-207, 2011.
5. Briggs DI, Enriori PJ, Lemus MB, Cowley MA, Andrews ZB. Dietinduced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons. Endocrinology 151: 4745-4755, 2010.
6. Castañeda TR, Tong J, Datta R, Culler M, Tschöp MH. Ghrelin in the regulation of body weight and metabolism. Front Neuroendocrinol 31: 44-60, 2010.
7. Chan CB, MacDonald PE, Saleh MC, Johns DC, Marban E, Wheeler MB. Overexpression of uncoupling protein 2 inhibits glucose-stimulated insulin secretion from rat islets. Diabetes 48: 1482-1486, 1999.
8. Chanoine JP, Wong AC, Barrios V. Obestatin, acylated and total ghrelin concentrations in the perinatal rat pancreas. Horm Res 66: 81-88, 2006.
9. Cheng K, Ho K, Stokes R, Scott C, Lau SM, Hawthorne WJ, O'Connell PJ, Loudovaris T, Kay TW, Kulkarni RN, Okada T, Wang XL, Yim SH, Shah Y, Grey ST, Biankin AV, Kench JG, Laybutt DR, Gonzalez FJ, Kahn CR, Gunton JE. Hypoxia-inducible factor-1alpha regulates beta cell function in mouse and human islets. J Clin Invest 120: 2171-2183, 2010.
10. Chmielewska J, Szczepankiewicz D, Skrzypski M, Kregielska D, Strowski MZ, Nowak KW. Ghrelin but not obestatin regulates insulin secretion from INS1 beta cell line via UCP2-dependent mechanism. J Biol Regul Homeost Agents 24: 397-402, 2010.
11. Chuang JC, Sakata I, Kohno D, Perello M, Osborne-Lawrence S, Repa JJ, Zigman JM. Ghrelin directly stimulates glucagon secretion from pancreatic alpha-cells. Mol Endocrinol 25: 1600-1611, 2011.
12. Cummings DE. Ghrelin and the short-and long-term regulation of appetite and body weight. Physiol Behav 89: 71-84, 2006.
13. da Silva Xavier G, Sun G, Qian Q, Rutter GA, Leclerc I. ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells. Biochem Biophys Res Commun 402: 252-257, 2010.
14. 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 alpha-cells of humans and rats and stimulates insulin secretion. Diabetes 51: 124-129, 2002.
15. Dentin R, Denechaud PD, Benhamed F, Girard J, Postic C. Hepatic gene regulation by glucose and polyunsaturated fatty acids: a role for ChREBP. J Nutr 136: 1145-1149, 2006.
16. Dezaki K, Sone H, Koizumi M, Nakata M, Kakei M, Nagai H, Hosoda H, Kangawa K, Yada T. Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance. Diabetes 55: 3486-3493, 2006.
17. Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, Bouillaud F, Seldin MF, Surwit RS, Ricquier D, Warden CH. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 15: 269-272, 1997.
18. Gauna C, Delhanty PJ, Hofland LJ, Janssen JA, Broglio F, Ross RJ, Ghigo E, van der Lely AJ. Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab 90: 1055-1060, 2005.
19. Gauna C, Kiewiet RM, Janssen JA, van de Zande B, Delhanty PJ, Ghigo E, Hofland LJ, Themmen AP, van der Lely AJ. Unacylated ghrelin acts as a potent insulin secretagogue in glucose-stimulated conditions. Am J Physiol Endocrinol Metab 293: E697-E704, 2007.
20. Granata R, Settanni F, Gallo D, Trovato L, Biancone L, Cantaluppi V, Nano R, Annunziata M, Campiglia P, Arnoletti E, Ghe C, Volante M, Papotti M, Muccioli G, Ghigo E. 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, 2008.
21. Heppner KM, Tong J, Kirchner H, Nass R, Tschöp MH. The ghrelin O-acyltransferase-ghrelin system: a novel regulator of glucose metabolism. Curr Opin Endocrinol Diabetes Obes 18: 50-55, 2011.
22. Hewson AK, Tung LY, Connell DW, Tookman L, Dickson SL. The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic. Diabetes 51: 3412-3419, 2002.
23. Hukshorn CJ, Saris WH. Leptin and energy expenditure. Curr Opin Clin Nutr Metab Care 7: 629-633, 2004.
24. Iwakura H, Akamizu T, Ariyasu H, Irako T, Hosoda K, Nakao K, Kangawa K. Effects of ghrelin administration on decreased growth hormone status in obese animals. Am J Physiol Endocrinol Metab 293: E819-E825, 2007.
25. 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 126: 67-71, 2005.
26. Lavine RL, Voyles N, Perrino PV, Recant L. Functional abnormalities of islets of Langerhans of obese hyperglycemic mouse. Am J Physiol Endocrinol Metab Gastrointest Physiol 233: E86-E90, 1977.
27. Lin L, Saha PK, Ma X, Henshaw IO, Shao L, Chang BH, Buras ED, Tong Q, Chan L, McGuinness OP, Sun Y. Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues. Aging Cell 10: 996-1010, 2011.
28. Lindström P. beta-cell function in obese-hyperglycemic mice [ob/ob Mice]. Adv Exp Med Biol 654: 463-477, 2010.
29. Longo KA, Charoenthongtrakul S, Giuliana DJ, Govek EK, McDonagh T, Qi Y, DiStefano PS, Geddes BJ. Improved insulin sensitivity and metabolic flexibility in ghrelin receptor knockout mice. Regul Pept 150: 55-61, 2008.
30. Ma X, Lin L, Qin G, Lu X, Fiorotto M, Dixit VD, Sun Y. Ablations of ghrelin and ghrelin receptor exhibit differential metabolic phenotypes and thermogenic capacity during aging. PLoS One 6: e16391, 2011.
31. Martinez SC, Tanabe K, Cras-Meneur C, Abumrad NA, Bernal-Mizrachi E, Permutt MA. Inhibition of Foxo1 protects pancreatic islet beta-cells against fatty acid and endoplasmic reticulum stress-induced apoptosis. Diabetes 57: 846-859, 2008.
32. Oberkofler H, Klein K, Felder TK, Krempler F, Patsch W. Role of peroxisome proliferator-activated receptor-gamma coactivator-1alpha in the transcriptional regulation of the human uncoupling protein 2 gene in INS-1E cells. Endocrinology 147: 966-976, 2006.
33. Obici S, Wang J, Chowdury R, Feng Z, Siddhanta U, Morgan K, Rossetti L. Identification of a biochemical link between energy intake and energy expenditure. J Clin Invest 109: 1599-1605, 2002.
34. Patel K, Dixit VD, Lee JH, Kim JW, Schaffer EM, Nguyen D, Taub DD. The GHS-R blocker D-[Lys3] GHRP-6 serves as CCR5 chemokine receptor antagonist. Int J Med Sci 9: 51-58, 2012.
35. Perello M, Scott MM, Sakata I, Lee CE, Chuang JC, Osborne-Lawrence S, Rovinsky SA, Elmquist JK, Zigman JM. Functional implications of limited leptin receptor and ghrelin receptor coexpression in the brain. J Comp Neurol 520: 281-294, 2012.
36. Poitout V, Robertson RP. An integrated view of beta-cell dysfunction in type-II diabetes. Annu Rev Med 47: 69-83, 1996.
37. Qader SS, Hakanson R, Rehfeld JF, Lundquist I, Salehi A. Proghrelinderived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas. Regul Pept 146: 230-237, 2008.
38. Rodríguez A, Gómez-Ambrosi J, Catalán V, Gil MJ, Becerril S, Sáinz N, Silva C, Salvador J, Colina I, Frühbeck G. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Int J Obes (Lond) 33: 541-552, 2009.
39. Rooth P, Taljedal IB. Vital microscopy of islet blood flow: catecholamine effects in normal and ob/ob mice. Am J Physiol Endocrinol Metab 252: E130-E135, 1987.
40. Saksida T, Stosic-Grujicic S, Timotijevic G, Sandler S, Stojanovic I. Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. Immunol Cell Biol. In press.
41. Salehi A, Dornonville de la Cour C, Håkanson R, Lundquist I. Effects of ghrelin on insulin and glucagon secretion: a study of isolated pancreatic islets and intact mice. Regul Pept 118: 143-150, 2004.
42. Soares JB, Leite-Moreira AF. Ghrelin, des-acyl ghrelin and obestatin: three pieces of the same puzzle. Peptides 29: 1255-1270, 2008.
43. Sun Y, Ahmed S, Smith RG. Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol 23: 7973-7981, 2003.
44. 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 3: 379-386, 2006.
45. Sun Y, Butte NF, Garcia JM, Smith RG. Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance. Endocrinology 149: 843-850, 2008.
46. 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 101: 4679-4684, 2004.
47. Szentirmai E, Kapas L, Sun Y, Smith RG, Krueger JM. The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice. Proc Natl Acad Sci USA 106: 14069-14074, 2009.
48. Thompson NM, Gill DA, Davies R, Loveridge N, Houston PA, Robinson IC, Wells T. Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 145: 234-242, 2004.
49. Tomita T, Doull V, Kimmel JR, Pollock HG. Pancreatic polypeptide and other hormones in pancreas of obese (ob/ob) mice. Diabetologia 27: 454-459, 1984.
50. 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 147: 2306-2314, 2006.
51. 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 87: 1300-1308, 2002.
52. Wente W, Efanov AM, Brenner M, Kharitonenkov A, Koster A, Sandusky GE, Sewing S, Treinies I, Zitzer H, Gromada J. Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes 55: 2470-2478, 2006.
53. 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 52: 301-310, 2004.
54. 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 115: 3573-3578, 2005.
55. Zavaroni I, Deferrari G, Lugari R, Bonora E, Garibotto G, Dall'Aglio E, Robaudo C, Gnudi A. Renal metabolism of C-peptide in man. J Clin Endocrinol Metab 65: 494-498, 1987.
56. 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, beta cell dysfunction, and type 2 diabetes. Cell 105: 745-755, 2001.
57. 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 310: 996-999, 2005.
58. Zhang W, Chai B, Li JY, Wang H, Mulholland MW. Effect of des-acyl ghrelin on adiposity and glucose metabolism. Endocrinology 149: 4710-4716, 2008.
59. Zhao TJ, Liang G, Li RL, Xie X, Sleeman MW, Murphy AJ, Valenzuela DM, Yancopoulos GD, Goldstein JL, Brown MS. Ghrelin Oacyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Proc Natl Acad Sci USA 107: 7467-7472, 2010.
60. Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, Jones JE, Deysher AE, Waxman AR, White RD, Williams TD, Lachey JL, Seeley RJ, Lowell BB, Elmquist JK. Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest 115: 3564-3572, 2005.