Low-dose ghrelin infusion - Evidence against a hormonal role in food intake

Regulatory Peptides

Volumn 174, Issue 1-3, 2012, Pages 26-31

  Lippl, Florian ^a   Erdmann, Johannes ^b   Steiger, Amelie ^a   Lichter, Nicole ^a   Czogalla Peter, Cäcilia ^a   Bidlingmaier, Martin ^a   Tholl, Sylvia ^b   Schusdziarra, Volker ^b  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

Food intake; Ghrelin; Hunger; Satiety

Indexed keywords

GHRELIN; GLUCOSE; GROWTH HORMONE; HYDROCORTISONE; PLACEBO; SODIUM CHLORIDE;

ADULT; ARTICLE; CALORIC INTAKE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG MECHANISM; FOOD ANALYSIS; FOOD INTAKE; GLUCOSE BLOOD LEVEL; GROWTH HORMONE BLOOD LEVEL; HORMONAL REGULATION; HUMAN; HUMAN EXPERIMENT; HUNGER; HYDROCORTISONE BLOOD LEVEL; LOW DRUG DOSE; MALE; NORMAL HUMAN; POSTPRANDIAL STATE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RATING SCALE; REACTION TIME; SATIETY; VISUAL ANALOG SCALE;

ADULT; BLOOD GLUCOSE; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; EATING; GHRELIN; GROWTH HORMONE; HUMANS; HUNGER; HYDROCORTISONE; INSULIN; MALE; SATIETY RESPONSE;

EID: 84856506002     PISSN: 01670115     EISSN: 18731686     Source Type: Journal    
DOI: 10.1016/j.regpep.2011.11.005     Document Type: Article

References (51)

1. 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.
2. Date Y., Kojima M., Hosoda H., Sawaguchi A., Mondal M., Suganuma T., Matsukura S., Kangawa K., Nakazato M. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distince endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 2000, 141:4255-4261.
3. Tschop M., Smiley D.L., Heiman M.L. Ghrelin induces adiposity in rodents. Nature 2000, 407:908-913.
4. Tschop M., Wawarta R., Riepl R.L., Friedrich S., Bidlingmaier M., Landgraf R., Folwaczny C. Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest 2001, 24:RC19-RC21.
5. Cummings D.E., Purnell J.Q., Frayo R.S., Schmidova K., Wisse B.E., Weigle D.S. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001, 50:1714-1719.
6. Shiiya T., Nakazato M., Mizuta M., Date Y., Mondal M.S., Tanaka M., Nozoe S., Hosoda H., Kangawa K., Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metabol 2002, 87:240-244.
7. Erdmann J., Lippl F., Schusdziarra V. Differential effect of protein and fat on plasma ghrelin levels in man. Regul Pept 2003, 116:101-107.
8. Tannous dit El Khoury D., Obeid O., Azar S.T., Hwalla N. Variations in postprandial ghrelin status following ingestion of high-carbohydrate, high-fat, and high-protein meals in males. Ann Nutr Metab 2006, 50:260-269.
9. Al Awar R., Obeid O., Hwalla N., Azar S. Postprandial acylated ghrelin status following fat and protein manipulation of meals in healthy young women. Clin Sci (Lond) 2005, 109:405-411.
10. Bednarek M.A., Feighner S.D., Pong S.S., McKee K.K., Hreniuk D.L., Silva M.V., Warren V.A., Howard A.D., Van der Ploeg L.H., Heck J.V. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J Med Chem 2000, 43:4370-4376.
11. Kojima M., Kangawa K. Ghrelin: structure and function. Physiol Rev 2005, 85:495-522.
12. Kirchner H., Gutierrez J.A., Solenberg P.J., Pfluger P.T., Czyzyk T.A., Willency J.A., Schurmann A., Joost H.G., Jandacek R.J., Hale J.E., Heiman M.L., Tschop M.H. GOAT links dietary lipids with the endocrine control of energy balance. Nat Med 2009, 15:741-745.
13. Akamizu T., Iwakura H., Ariyasu H., Hosoda H., Murayama T., Yokode M., Teramukai S., Seno H., Chiba T., Noma S., Nakai Y., Fukunaga M., Kangawa K. Repeated administration of ghrelin to patients with functional dyspepsia: its effects on food intake and appetite. Eur J Endocrinol 2008, 158:491-498. Team FDCS.
14. Adachi S., Takiguchi S., Okada K., Yamamoto K., Yamasaki M., Miyata H., Nakajima K., Fujiwara Y., Hosoda H., Kangawa K., Mori M., Doki Y. Effects of ghrelin administration after total gastrectomy: A prospective randomized placebo-controlled phase II study. Gastroenterology 2010, 138:1312-1320.
15. Ang D., Nicolai H., Vos R., Mimidis K., Akyuz F., Kindt S., Vanden B.P., Sifrim D., Depoortere I., Peeters T., Tack J. Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man. Neurogastroenterol Motil 2009, 76:199-206.
16. Schmid D.A., Held K., Ising M., Uhr M., Weikel J.C., Steiger A. Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls. Neuropsychopharmacology 2005, 30:1187-1192.
17. Hotta M., Ohwada R., Akamizu T., Shibasaki T., Takano K., Kangawa K. Ghrelin increases hunger and food intake in patients with restricting-type anorexia nervosa: a pilot study. Endocr J 2009, 56:1119-1128.
18. Ashby D.R., Ford H.E., Wynne K.J., Wren A.M., Murphy K.G., Busbridge M., Brown E.A., Taube D.H., Ghatei M.A., Tam F.W., Bloom S.R., Choi P. Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment. Kidney Int 2009, 22:192-200.
19. Benso A., Gramaglia E., Prodam F., Riganti F., Gigliardi V.R., Lucatello B., Olivetti I., St Pierre D., Ghigo E., Broglio F. Beta-adrenergic agonism does not impair the GH response to acylated ghrelin in humans. Clin Endocrinol (Oxf) 2009, 71:234-236.
20. Huda M.S., Dovey T., Wong S.P., English P.J., Halford J., McCulloch P., Cleator J., Martin B., Cashen J., Hayden K., Wilding J.P., Pinkney J. Ghrelin restores 'lean-type' hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects. Int J Obes (Lond) 2009, 33:317-325.
21. Vestergaard E.T., Hansen T.K., Gormsen L.C., Jakobsen P., Moller N., Christiansen J.S., Jorgensen J.O. Constant intravenous ghrelin infusion in healthy young men: clinical pharmacokinetics and metabolic effects. Am J Physiol Endocrinol Metab 2007, 292:E1829-E1836.
22. Levin F., Edholm T., Schmidt P.T., Gryback P., Jacobsson H., Degerblad M., Hoybye C., Holst J.J., Rehfeld J.F., Hellstrom P.M., Naslund E. Ghrelin stimulates gastric emptying and hunger in normal-weight humans. J Clin Endocrinol Metab 2006, 91:3296-3302.
23. Wren A.M., Seal L.J., Cohen M.A., Brynes A.E., Frost G.S., Murphy K.G., Dhillo W.S., Ghatei M.A., Bloom S.R. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001, 86:5992-5995.
24. Falken Y., Hellstrom P.M., Sanger G.J., Dewit O., Dukes G., Gryback P., Holst J.J., Naslund E. Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans. Neurogastroenterol Motil 2010.
25. Druce M.R., Wren A.M., Park A.J., Milton J.E., Patterson M., Frost G., Ghatei M.A., Small C., Bloom S.R. Ghrelin increases food intake in obese as well as lean subjects. Int J Obes (Lond) 2005, 29:1130-1136.
26. Murray C.D., Martin N.M., Patterson M., Taylor S.A., Ghatei M.A., Kamm M.A., Johnston C., Bloom S.R., Emmanuel A.V. Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study. Gut 2005, 54:1693-1698.
27. Huda M.S., Durham B.H., Wong S.P., Dovey T.M., McCulloch P., Kerrigan D., Pinkney J.H., Fraser W.D., Wilding J.P. Lack of an acute effect of ghrelin on markers of bone turnover in healthy controls and post-gastrectomy subjects. Bone 2007, 41:406-413.
28. Kiewiet R.M., van Aken M.O., van der Weerd K., Uitterlinden P., Themmen A.P., Hofland L.J., de Rijke Y.B., Delhanty P.J., Ghigo E., Abribat T., van der Lely A.J. Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes. Eur J Endocrinol 2009, 161:567-573.
29. Paulo R.C., Brundage R., Cosma M., Mielke K.L., Bowers C.Y., Veldhuis J.D. Estrogen elevates the peak overnight production rate of acylated ghrelin. J Clin Endocrinol Metab 2008, 93:4440-4447.
30. Veldhuis J.D., Reynolds G.A., Iranmanesh A., Bowers C.Y. Twenty-four hour continuous ghrelin infusion augments physiologically pulsatile, nycthemeral, and entropic (feedback-regulated) modes of growth hormone secretion. J Clin Endocrinol Metab 2008, 93:3597-3603.
31. Miljic D., Pekic S., Djurovic M., Doknic M., Milic N., Casanueva F.F., Ghatei M., Popovic V. Ghrelin has partial or no effect on appetite, growth hormone, prolactin, and cortisol release in patients with anorexia nervosa. J Clin Endocrinol Metab 2006, 91:1491-1495.
32. Neary N.M., Small C.J., Wren A.M., Lee J.L., Druce M.R., Palmieri C., Frost G.S., Ghatei M.A., Coombes R.C., Bloom S.R. Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2004, 89:2832-2836.
33. Cummings D.E., Frayo R.S., Marmonier C., Aubert R., Chapelot D. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am J Physiol Endocrinol Metab 2004, 287:E297-E304.
34. Erdmann J., Topsch R., Lippl F., Gussmann P., Schusdziarra V. Postprandial response of plasma ghrelin levels to various test meals in relation to food intake, plasma insulin, and glucose. J Clin Endocrinol Metab 2004, 89:3048-3054.
35. Erdmann J., Hebeisen Y., Lippl F., Wagenpfeil S., Schusdziarra V. Food intake and plasma ghrelin response during potato-, rice- and pasta-rich test meals. Eur J Nutr 2007, 46:196-203.
36. Grossman M.I. Physiological effects of gastrointestinal hormones. Fed Proc 1977, 36:1930-1932.
37. Schusdziarra V., Lawecki J., Ditschuneit H.H., Lukas B., Maier V., Pfeiffer E.F. Effect of low-dose somatostatin infusion on pancreatic and gastric endocrine function in lean and obese nondiabetic human subjects. Diabetes 1985, 34:595-601.
38. Zimmerhackl B., Wunsch E., Classen M., Schusdziarra V., Schepp W. In man histamine and muscarinergic mechanisms are essential mediators of acid secretion in response to synthetic human gastrin (1-17). Regul Pept 1993, 46:583-592.
39. Gauna C., Meyler F.M., Janssen J.A., Delhanty P.J., Abribat T., van Koetsveld P., Hofland L.J., Broglio F., Ghigo E., van der Lely A.J. 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.
40. Sturm K., MacIntosh C.G., Parker B.A., Wishart J., Horowitz M., Chapman I.M. Appetite, food intake, and plasma concentrations of cholecystokinin, ghrelin, and other gastrointestinal hormones in undernourished older women and well-nourished young and older women. J Clin Endocrinol Metab 2003, 88:3747-3755.
41. Sun Y., Ahmed S., Smith R.G. Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol 2003, 23:7973-7981.
42. Wortley K.E., Anderson K.D., Garcia K., Murray J.D., Malinova L., Liu R., Moncrieffe M., Thabet K., Cox H.J., Yancopoulos G.D., Wiegand S.J., Sleeman M.W. Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci U S A 2004, 101:8227-8232.
43. Haqq A.M., Farooqi I.S., O'Rahilly S., Stadler D.D., Rosenfeld R.G., Pratt K.L., LaFranchi S.H., Purnell J.Q. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in prader-willi syndrome. J Clin Endocrinol Metab 2003, 88:174-178.
44. Masuda Y., Tanaka T., Inomata N., Ohnuma N., Tanaka S., Itoh Z., Hosoda H., Kojima M., Kangawa K. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 2000, 276:905-908.
45. Dornonville de la Cour C., Lindstrom E., Norlen P., Hakanson R. Ghrelin stimulates gastric emptying but is without effect on acid secretion and gastric endocrine cells. Regul Pept 2004, 120:23-32.
46. Sallam H.S., Oliveira H.M., Gan H.T., Herndon D.N., Chen J.D. Ghrelin improves burn-induced delayed gastrointestinal transit in rats. Am J Physiol Regul Integr Comp Physiol 2007, 292:R253-R257.
47. Chen Y.T., Tsai S.H., Sheu S.Y., Tsai L.H. Ghrelin improves LPS-induced gastrointestinal motility disturbances: roles of NO and prostaglandin E2. Shock 2010, 33:205-212.
48. Malagelada J.R., Longstreth G.F., Summerskill W.H., Go V.L. Measurement of gastric functions during digestion of ordinary solid meals in man. Gastroenterology 1976, 70:203-210.
49. 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 Regul Integr Comp Physiol 2001, 280:R1483-R1487.
50. Vestergaard E.T., Andersen N.H., Hansen T.K., Rasmussen L.M., Moller N., Sorensen K.E., Sloth E., Jorgensen J.O. Cardiovascular effects of intravenous ghrelin infusion in healthy young men. Am J Physiol Heart Circ Physiol 2007, 293:H3020-H3026.
51. Broglio F., Arvat E., Benso A., Gottero C., Muccioli G., Papotti M., van der Lely A.J., 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.