GPR39, a receptor of the ghrelin receptor family, plays a role in the regulation of glucose homeostasis in a mouse model of early onset diet-induced obesity

Journal of Neuroendocrinology

Volumn 23, Issue 6, 2011, Pages 490-500

  Verhulst, P J ^a   Lintermans, A ^a   Janssen, S ^a   Loeckx, D ^b   Himmelreich, U ^c   Buyse, J ^d   Tack, J ^a   Depoortere, I ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c KU Leuven   (Belgium)

^d LABORATORY OF GENE TECHNOLOGY   (Belgium)

Author keywords

Diet induced obesity; Gastric emptying; Glucose; GPR39; Insulin

Indexed keywords

GHRELIN RECEPTOR; GLUCOSE; GPR39 RECEPTOR; INSULIN; MESSENGER RNA; UNCLASSIFIED DRUG; ZINC;

ADIPOSE TISSUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD EXAMINATION; BODY FAT DISTRIBUTION; BODY WEIGHT; CALORIC INTAKE; CLINICAL EVALUATION; CONTROLLED STUDY; CORRELATION ANALYSIS; DIET RESTRICTION; EARLY ONSET DIET INDUCED OBESITY; ENERGY BALANCE; GENE EXPRESSION; GENOTYPE; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE TEST; IMMUNOFLUORESCENCE TEST; IMMUNOHISTOCHEMISTRY; INSULIN BLOOD LEVEL; INSULIN SENSITIVITY; LIPID DIET; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OBESITY; PANCREAS ISLET CELL HYPERPLASIA; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; RECEPTOR DOWN REGULATION; REGULATORY MECHANISM; RESPIRATORY QUOTIENT; STOMACH EMPTYING;

AGE OF ONSET; ANIMALS; DIABETES MELLITUS, TYPE 2; DIET; DIET, ATHEROGENIC; DISEASE MODELS, ANIMAL; GENETIC PREDISPOSITION TO DISEASE; GLUCOSE; HOMEOSTASIS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MULTIGENE FAMILY; OBESITY; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, GHRELIN;

EID: 79955978919     PISSN: 09538194     EISSN: 13652826     Source Type: Journal    
DOI: 10.1111/j.1365-2826.2011.02132.x     Document Type: Article

References (44)

1. McKee KK, Tan CP, Palyha OC, Liu J, Feighner SD, Hreniuk DL, Smith RG, Howard AD, Van der Ploeg LH. Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors. Genomics 1997; 46: 426-434.
2. 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.
3. Lagaud GJ, Young A, Acena A, Morton MF, Barrett TD, Shankley NP. Obestatin reduces food intake and suppresses body weight gain in rodents. Biochem Biophys Res Commun 2007; 357: 264-269.
4. De Smet B, Thijs T, Peeters TL, Depoortere I. Effect of peripheral obestatin on gastric emptying and intestinal contractility in rodents. Neurogastroenterol Motil 2007; 19: 211-217.
5. Depoortere I, Thijs T, Moechars D, De Smet B, Ver Donck L, Peeters TL. Effect of peripheral obestatin on food intake and gastric emptying in ghrelin-knockout mice. Br J Pharmacol 2008; 153: 1550-1557.
6. Nogueiras R, Pfluger P, Tovar S, Arnold M, Mitchell S, Morris A, Perez-Tilve D, Vazquez MJ, Wiedmer P, Castaneda TR, DiMarchi R, Tschop M, Schurmann A, Joost HG, Williams LM, Langhans W, Dieguez C. Effects of obestatin on energy balance and growth hormone secretion in rodents. Endocrinology 2007; 148: 21-26.
7. Gourcerol G, St-Pierre DH, Tache Y. Lack of obestatin effects on food intake: should obestatin be renamed ghrelin-associated peptide (GAP)? Regul Pept 2007; 3: 1-7.
8. Kobelt P, Wisser AS, Stengel A, Goebel M, Bannert N, Gourcerol G, Inhoff T, Noetzel S, Wiedenmann B, Klapp BF, Tache Y, Monnikes H. Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents. Peptides 2008; 29: 1018-1027.
9. Chartrel N, Alvear-Perez R, Leprince J, Iturrioz X, Reaux-Le Goazigo A, Audinot V, Chomarat P, Coge F, Nosjean O, Rodriguez M, Galizzi JP, Boutin JA, Vaudry H, Llorens-Cortes C. Comment on 'Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake'. Science 2007; 315: 766.
10. Lauwers E, Landuyt B, Arckens L, Schoofs L, Luyten W. Obestatin does not activate orphan G protein-coupled receptor GPR39. Biochem Biophys Res Commun 2006; 351: 21-25.
11. Holst B, Egerod KL, Schild E, Vickers SP, Cheetham S, Gerlach LO, Storjohann L, Stidsen CE, Jones R, Beck-Sickinger AG, Schwartz TW. GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology 2007; 148: 13-20.
12. 2+ as an endogenous agonist of GPR39 from fetal bovine serum. J Recept Signal Transduct Res 2007; 27: 235-246.
13. Moechars D, Depoortere I, Moreaux B, de Smet B, Goris I, Hoskens L, Daneels G, Kass S, Ver Donck L, Peeters T, Coulie B. Altered gastrointestinal and metabolic function in the GPR39-obestatin receptor-knockout mouse. Gastroenterology 2006; 131: 1131-1141.
14. Egerod KL, Holst B, Petersen PS, Hansen JB, Mulder J, Hokfelt T, Schwartz TW. GPR39 splice variants versus antisense gene LYPD1: expression and regulation in gastrointestinal tract, endocrine pancreas, liver, and white adipose tissue. Mol Endocrinol 2007; 21: 1685-1698.
15. Catalan V, Gomez-Ambrosi J, Rotellar F, Silva C, Gil MJ, Rodriguez A, Cienfuegos JA, Salvador J, Fruhbeck G. The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2007; 66: 598-601.
16. Quarterman J, Mills CF, Humphries WR. The reduced secretion of, and sensitivity to insulin in zinc-deficient rats. Biochem Biophys Res Commun 1966; 25: 354-358.
17. Simon SF, Taylor CG. Dietary zinc supplementation attenuates hyperglycemia in db/db mice. Exp Biol Med (Maywood) 2001; 226: 43-51.
18. Begin-Heick N, Dalpe-Scott M, Rowe J, Heick HM. Zinc supplementation attenuates insulin secretory activity in pancreatic islets of the ob/ob mouse. Diabetes 1985; 34: 179-184.
19. Chen MD, Liou SJ, Lin PY, Yang VC, Alexander PS, Lin WH. Effects of zinc supplementation on the plasma glucose level and insulin activity in genetically obese (ob/ob) mice. Biol Trace Elem Res 1998; 61: 303-311.
20. Winzell MS, Ahren B. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 2004; 53(Suppl. 3): S215-S219.
21. Buyse J, Michels H, Vloeberghs J, Saevels P, Aerts JM, Ducro B, Berckmans D, Decuypere E. Energy and protein metabolism between 3 and 6weeks of age of male broiler chickens selected for growth rate or for improved food efficiency. Br Poult Sci 1998; 39: 264-272.
22. Andrikopoulos S, Blair AR, Deluca N, Fam BC, Proietto J. Evaluating the glucose tolerance test in mice. Am J Physiol Endocrinol Metab 2008; 295: E1323-E1332.
23. Kitazawa T, De Smet B, Verbeke K, Depoortere I, Peeters TL. Gastric motor effects of peptide and non-peptide ghrelin agonists in mice in vivo and in vitro. Gut 2005; 54: 1078-1084.
24. Astrup A. The role of dietary fat in the prevention and treatment of obesity. Efficacy and safety of low-fat diets. Int J Obes Relat Metab Disord 2001; 25(Suppl. 1): S46-S50.
25. Tremblay F, Richard AM, Will S, Syed J, Stedman N, Perreault M, Gimeno RE. Disruption of G protein-coupled receptor 39 impairs insulin secretion in vivo. Endocrinology 2009; 150: 2586-2595.
26. Holst B, Egerod KL, Jin C, Petersen PS, Ostergaard MV, Hald J, Sprinkel AM, Storling J, Mandrup-Poulsen T, Holst JJ, Thams P, Orskov C, Wierup N, Sundler F, Madsen OD, Schwartz TW. G protein-coupled receptor 39 deficiency is associated with pancreatic islet dysfunction. Endocrinology 2009; 150: 2577-2585.
27. Holst B, Egerod KL, Jin C, Petersen PS, Ostergaard MV, Hald J, Sprinkel AM, Storling J, Mandrup-Poulsen T, Holst JJ, Thams P, Orskov C, Wierup N, Sundler F, Madsen OD, Schwartz TW. GPR39 deficiency is associated with pancreatic islet dysfunction. Endocrinology 2009; 150: 2577-2585.
28. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707-709.
29. 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.
30. 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.
31. Reimer MK, Pacini G, Ahren B. Dose-dependent inhibition by ghrelin of insulin secretion in the mouse. Endocrinology 2003; 144: 916-921.
32. 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.
33. 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.
34. Theander-Carrillo C, Wiedmer P, Cettour-Rose P, Nogueiras R, Perez-Tilve D, Pfluger P, Castaneda TR, Muzzin P, Schurmann A, Szanto I, Tschop MH, Rohner-Jeanrenaud F. Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 2006; 116: 1983-1993.
35. Tschop M, Statnick MA, Suter TM, Heiman ML. GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein. Endocrinology 2002; 143: 558-568.
36. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407: 908-913.
37. De Smet B, Depoortere I, Moechars D, Swennen Q, Moreaux B, Cryns K, Tack J, Buyse J, Coulie B, Peeters TL. Energy homeostasis and gastric emptying in ghrelin knockout mice. J Pharmacol Exp Ther 2006; 316: 431-439.
38. 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.
39. 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 2005; 115: 3564-3572.
40. Heijboer AC, van den Hoek AM, Parlevliet ET, Havekes LM, Romijn JA, Pijl H, Corssmit EP. Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice. Diabetologia 2006; 49: 732-738.
41. 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 2001; 105: 745-755.
42. Affourtit C, Brand MD. Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion. Biochem J 2008; 409: 199-204.
43. Krauss S, Zhang CY, Scorrano L, Dalgaard LT, St-Pierre J, Grey ST, Lowell BB. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest 2003; 112: 1831-1842.
44. Huang XF, Arvan P. Intracellular transport of proinsulin in pancreatic beta-cells. Structural maturation probed by disulfide accessibility. J Biol Chem 1995; 270: 20417-20423.