help button home button Endocrine Society JCEM JCEM Call for Nominations for EIC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arosio, M.
Right arrow Articles by Peracchi, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arosio, M.
Right arrow Articles by Peracchi, M.
The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 10 5101-5104
Copyright © 2004 by The Endocrine Society

Effects of Modified Sham Feeding on Ghrelin Levels in Healthy Human Subjects

Maura Arosio, Cristina L. Ronchi, Paolo Beck-Peccoz, Carlotta Gebbia, Claudia Giavoli, Vincenzo Cappiello, Dario Conte and Maddalena Peracchi

Institute of Endocrine Sciences (M.A., C.L.R., P.B.-P., C.Gi., V.C.) and Department of Medical Sciences (C.Ge., D.C., M.P.), University of Milan, Ospedale Maggiore IRCCS, and Department of Endocrinology, Ospedale S. Giuseppe-Fatebenefratelli A.FaR. (M.A.), I 20123 Milan, Italy

Address all correspondence and requests for reprints to: Dr. Maura Arosio, Department of Endocrinologia, Ospedale S. Giuseppe-FatebeneFratelli, Via S. Vittore 12, I 20123 Milan, Italy. E-mail: maura.arosio{at}unimi.it.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
The mechanisms involved in the preprandial rise and postprandial fall of circulating ghrelin levels are as yet unknown. Many hormonal and metabolic responses to nutrient intake begin during the cephalic or preabsorptive phase and are mostly mediated by the autonomous nervous system. The aim of the present study was to investigate the effects of the cephalic phase on ghrelin response to feeding in human subjects. The modified sham feeding (MSF), a well established technique in which nutrients are smelled, chewed, and tasted, but not swallowed, was used. Sixteen healthy volunteers (seven men and nine women; mean age ± SD: 31 ± 8 yr; body mass index, 22 ± 3 kg/m2) were studied after overnight fasting. Seven of them received a standardized mixed meal, and nine underwent MSF. Blood samples for ghrelin, insulin, and glucose were taken at time –30, 0, 15, 30, 45, 60, 120 min during both tests. Pancreatic polypeptide determinations were evaluated at all times as markers of vagal activity only during MSF. Ghrelin levels significantly increased from time –30 to 0 min before the two tests, then significantly decreased: after the real feeding from 933 ± 479 pg/ml (277 ± 142 pmol/liter) to 455 ± 185 pg/ml (135 ± 55 pmol/liter; P < 0.05), and after the sham feeding from 917 ± 313 pg/ml (272 ± 93 pmol/liter) to 519 ± 261 pg/ml (154 ± 77 pmol/liter; P < 0.05). There were no significant differences between the patterns of the responses as evaluated by ANOVA (P = 0.863). As expected after MSF, plasma pancreatic polypeptide concentrations promptly increased from 58 ± 29 pg/ml (14 ± 7 pmol/liter) to 113 ± 38 pg/ml (27 ± 9 pmol/liter) at 15 min (P < 0.01). Both insulin and glucose levels increased during the actual mixed meal, whereas they were not significantly modified by MSF. In conclusion, circulating ghrelin concentrations are decreased by sham feeding as they are by real feeding in humans. These findings underline the importance of the cephalic response to nutrient intake, i.e. the role of vagal activity, in the control of ghrelin secretion.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
GHRELIN IS A GUT-BRAIN hormone involved in the control of energy homeostasis with orexigenic, endocrine, and gastro-entero-pancreatic (GEP) effects (1, 2, 3, 4). Ghrelin is mainly secreted from the stomach (5), and preprandial rises and postprandial falls in circulating peptide levels have been described in animals and humans (6, 7, 8, 9), but the mechanisms governing these responses are still largely unknown. Autonomic nervous system stimulation and hormone secretion participate in the control of gastrointestinal responses to nutrient intake; these are usually subdivided into cephalic, gastric, and intestinal phases. In humans, the preabsorptive cephalic phase response results from smell, sight, and oropharyngeal stimuli of palatable food. This response consists mostly of vagal efferent activation and concomitant release of some GEP hormones, and it may influence the subsequent gastrointestinal responses (10, 11, 12). A role for cephalic-vagal stimulation in the control of the ghrelin meal-related changes has been recently suggested by the finding that in sheep, pseudo-feeding (i.e. a meal enveloped by nylon bag that cannot be eaten) and actual feeding result in qualitatively similar peptide responses (7). However, different results have been reported in humans (13). Therefore, we decided to verify in healthy subjects the effects on ghrelin levels of cephalic stimulation achieved by the modified sham feeding (MSF), or "chew and spit" technique, in which foods are smelled, chewed, and tasted, but not swallowed (14). The plasma pancreatic polypeptide (PP) response to MSF was assayed as an indicator of successful vagal activity (15). Ghrelin results were compared with those obtained with a real feeding.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Sixteen healthy subjects of normal weight recruited among medical staff [seven men and nine women; mean ± SD age, 31 ± 9 yr; body mass index (BMI), 22 ± 3 kg/m2] volunteered for this study, which was approved by the Ospedale Maggiore ethics committee. All subjects had normal physical examination and no history of gastrointestinal or endocrine disorders. Nine of them (four men and five women; age, 28 ± 3 yr; BMI, 22 ± 4 kg/m2) underwent the MSF, and seven (three men and four women; age, 33 ± 11 yr; BMI, 22 ± 2 kg/m2; not significant vs. MSF group data) underwent a real feeding by giving them the same mixed meal. Every subject knew in advance the test for which he had been scheduled and the procedure details.

Procedures

The studies were carried out in the postabsorptive state; they started between 0900 and 0930 h after overnight fasting and 1 h of rest. The test meal, consisting of white bread (90 g), lean ham (70 g), one egg, olive oil (10 g), orange juice (100 ml), and water ad libitum (550 kcal; 48% carbohydrate, 33% fat, 19% and protein), was given at 0 min and eaten in 15 min in the actual feeding study. In the MSF study, for 15 min the same meal was smelled, put into the mouth, chewed, tasted, and then spat out, instead of being swallowed. Blood samples were taken at –30, 0, 15, 30, 60, 90, and 120 min from a forearm through a venous cannula that was kept patent by slow saline infusion. Serum samples for ghrelin and insulin assays and plasma samples for glucose measurements were collected at each time point, separated at room temperature, and stored at –20 C. Plasma samples for PP assay in the MSF study were collected in ice-chilled polypropylene tubes containing EDTA (1 mg/ml) and aprotinin (500 kallikrein inhibitor units/ml), separated immediately by centrifugation at 4 C, and stored in aliquots at –80 C until assayed.

Methods

Plasma PP and serum ghrelin levels were measured as previously described (3) using commercially available kits (PP: Peninsula Laboratories, Inc., San Carlos, CA; ghrelin: Phoenix Pharmaceuticals, Inc., Belmont, CA). The antibody employed for ghrelin assay detected acylated, bioactive, and des-acyl, bioinactive forms of the hormone. Serum insulin levels were determined by ELISA (Medgenix-Ins-EASIA, BioSource Technologies, Inc., Europe, Nivelles, Belgium), and plasma glucose concentrations were determined by glucose autoanalyzer with the hexokinase method (Beckman, Milan, Italy). The intra- and interassay coefficients of variation were less than 10% for all methods.

Statistical analysis

Except when otherwise noted, the results are expressed as the mean ± SD. Significant differences in mean levels of hormones among sampling times were assessed by one-way ANOVA for repeated measures, followed by Student-Newman-Keuls post hoc test. The comparison between the time courses of ghrelin after the two tests was carried out using a two-way ANOVA for repeated measures. A t test, for paired or unpaired data as appropriate, was used for comparisons between two variables. Correlation coefficients were calculated by linear regression analysis. P < 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The results are summarized in Table 1Go and Figs. 1Go and 2Go. Circulating ghrelin levels significantly decreased after both actual and sham feedings (Fig. 1Go). There was no significant difference in the nadir values. However, as shown in Table 1Go, the nadir occurred significantly earlier after MSF than after the actual meal (range, 15–60 vs. 90–120 min, respectively; P<0.01). Also at 120 min ghrelin levels returned to the fasting values (–30 min) after MSF, whereas they were still suppressed after the actual meal (Fig. 1Go). Nevertheless, the postprandial concentration-time curves of ghrelin did not significantly differ in the two studies at any point (P = 0.863).


View this table:
[in this window]
[in a new window]
  		TABLE 1. Pattern of ghrelin in response to actual feeding and/or MSF

 


View larger version (14K):
[in this window]
[in a new window]
  		FIG. 1. Pattern of ghrelin levels expressed as the mean ± SE before and after MSF ({blacksquare}) and actual feeding ({triangleup}). For picomoles per liter, divide by 3.37. *, P < 0.05; **, P < 0.01 (vs. 0 min for MSF). °, P < 0.05; °°, P < 0.01 (vs. 0 min for actual feeding).

 


View larger version (12K):
[in this window]
[in a new window]
  		FIG. 2. Pattern of PP plasma levels expressed as the mean ± SE before and after MSF. For picomoles per liter, divide by 4.179. *, P < 0.05; **, P < 0.01 (vs. 0 min).

 
After MSF, plasma PP levels promptly increased from 58 ± 29 pg/ml (14 ± 7 pmol/liter) to a peak of 113 ± 38 pg/ml (27 ± 9 pmol/liter; P < 0.01) at 15 min, with a net increment higher than 42 pg/ml (10 pmol/liter) within 30 min in all subjects (Fig. 2Go). A positive linear correlation was seen between the magnitude of the two responses to MSF, that is between {Delta} ghrelin decreases, calculated on the nadir values, and {Delta} PP increases, calculated on the peak values (r2= 0.53; P < 0.05).

Both glucose and insulin levels significantly increased after the real feeding, whereas they were not significantly modified by the sham feeding and remained in the fasting range throughout the study period (Table 1Go).

It is of interest that fasting baseline ghrelin levels significantly increased from –30 to 0 min in all study participants without significant differences between subjects scheduled for MSF and actual feeding (Table 1Go and Fig. 1Go).


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
This study demonstrates for the first time in humans that the meal-related changes in circulating ghrelin, including both the preprandial rise and the postprandial fall, can also be induced by sham feeding, i.e. without food ingestion. In our subjects the ghrelin surges just before MSF and actual feeding were similar, as were the subsequent nadir values; however, the postprandial ghrelin fall was rapid and transient after MSF and progressive and sustained after the mixed meal. Similar results have been previously reported in scheduled meal-fed sheep with actual and pseudo-feeding (7). However, our data contrast with those reported by Erdmann et al. (13), who did not find a ghrelin response in human subjects after either a breakfast MSF or ingestion of nonnutritive guar. Nevertheless, Nedvidkova et al. (16) demonstrated that in humans, oral ingestion of nonnutritive fiber suppresses ghrelin levels in the same way as does food ingestion. Moreover, Heath et al. (17) recently found that in healthy subjects the fall in ghrelin after fat ingestion is markedly enhanced by a previous MSF and occurs more rapidly. The reasons for these discrepancies are unclear. On the other hand, in all our subjects and those studied by Heath et al. (17), MSF induced a significant increase in PP concentrations, which is a reliable indicator of successful cephalic stimulation (15), whereas the PP pattern was not evaluated in Erdmann’s study (13). In our and other (13, 17, 18) studies, the lack of changes in insulin and glucose after MSF make unlikely the possibility of inadvertent swallowing. Thus, the ghrelin response to MSF is really due to actual cephalic stimulation and could result from the vagal stimulation achieved by this technique (14). This hypothesis is also consistent with the positive correlation between the net decrease in ghrelin and the net increase in PP found in the present study.

The precise role of the efferent vagal system and the possible relevance of vago-vagal reflexes (19) in the control of human ghrelin secretion remain to be elucidated. Vagal fibers arrive in the neighborhood of the oxyntic glands of the stomach, where the ghrelin-producing cells are primarily located. In rodents, electrical stimulation of the vagus nerve tends to decrease bioactive acyl ghrelin levels (20). Moreover, some data show that plasma ghrelin levels increase in rats after vagotomy (21), although opposite results were recently reported (22). In sheep, the infusion of the muscarinic cholinergic blockers atropine increases circulating ghrelin levels and abolishes the physiological postprandial ghrelin decrease (23) despite the fact that in humans pirenzepine, a specific M1 antagonist, has been recently reported to decrease fasting morning ghrelin concentrations (24).

Our results with MSF better support the hypothesis that in human subjects given an actual meal, the vagally mediated cephalic phase has a major role in initiating the postprandial fall in ghrelin levels, which are thereafter maintained suppressed by other, incompletely known, gastrointestinal or postabsorptive mechanisms, mediating the nutrient-related response. The gastric phase alone appears to play no role in the regulation of ghrelin secretion, because neither gastric distension alone nor activation of gastric chemical sensation modifies ghrelin levels (13, 25, 26). On the contrary, it has been suggested that the type of ingested macronutrient could influence the magnitude and pattern of ghrelin response during the intestinal phase (13, 27). This mechanism implies that either direct nutrient luminal stimulation or increased circulating nutrient concentrations or GEP hormones released by ingested food could modulate ghrelin secretion. In humans, the direct and indirect potential importance of amino acids and lipids remains to be clarified, whereas a role for postprandial hyperglycemia and/or hyperinsulinemia has been suggested. Indeed, both oral and iv glucose administration have been shown to decrease circulating ghrelin levels (26, 28, 29, 30), and prolonged, but not acute, insulin infusion suppressed ghrelin levels in euglycemic, hypoglycemic, and hyperglycemic states achieved by the glucose clamp procedure (31, 32, 33, 34). In this respect, it is noteworthy that we did not find any modification in glucose and insulin concentrations after MSF. A similar observation was made using a different protocol (fat meal) by Heath et al. (17). A role for systemic somatostatin in the postprandial control of ghrelin has been hypothesized, because its infusion inhibits ghrelin release (35, 36, 37, 38). Moreover, in the gastric oxyntic mucosa of rats, the somatostatin-immunoreactive cells contact ghrelin-immunoreactive cells (36), a finding suggestive of a paracrine effect for somatostatin in the control of ghrelin secretion in addition to the above putative endocrine role.

Finally, it is of interest that the well known premeal ghrelin surge also occurred just before MSF. The precise nature of neural and/or hormonal mechanisms that account for this elevation remains to be determined. Because ghrelin is an orexigenic hormone, it is tempting to speculate a physiological role for this hormone in the short-term control of premeal hunger and meal initiation, probably due to a conditioned physiological reflex (8, 7, 38, 39). The participants in our study knew whether they had been scheduled for MSF or an actual meal, but the ghrelin increments were similar for both studies. These data could suggest that in healthy subjects there is an anticipatory response to the orosensorial stimulation by palatable foods, but additional studies are required to clarify these issues as well as the underlying mechanisms. Vagal mediation has been shown to be operative in rat for the long-term food deprivation-induced elevation of plasma ghrelin (21, 22, 40). However, in healthy men, complete fasting for 3 d did not significantly increase 24-h ghrelin levels (41). Moreover, in our study the short-term response to the expectation of food does not seem to involve vagal efferent activation, as shown by the lack of PP modifications before the sham feeding.

In conclusion, acute changes in serum ghrelin levels in response to meals may also be elicited by the cephalic phase only. Although the mechanisms involved remain to be elucidated, these results favor a role for vagal involvement in the initial postmeal ghrelin fall in humans.


   Acknowledgments
 
We thank Drs. Simona Pizzinelli and Ciro Vescarelli for hormone measurements, and Mrs. Rita Deriu for nursing assistance. We are indebted to Dr. Iacopo Chiodini and Paolo Bucciarelli for their help with statistical analysis.


   Footnotes
 
This work was supported in part by research grants from Fondo Interno Ricerca Scientifica e Technologica funds of University of Milan and from Associazione Amici della Gastroenterologia del Padiglione Granelli (Milan, Italy).

Abbreviations: BMI, Body mass index; GEP, gastro-entero-pancreatic; MSF, modified sham feeding; PP, pancreatic polypeptide.

Received December 30, 2003.

Accepted July 10, 2004.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K 1999 Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660[CrossRef][Medline]
  2. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR 2001 Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:5992–5997[Abstract/Free Full Text]
  3. Arosio M, Ronchi CL, Gebbia C, Cappiello V, Beck-Peccoz P, Peracchi M 2003 Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. J Clin Endocrinol Metab 88:701–704[Abstract/Free Full Text]
  4. Muccioli G, Tshöp M, Papotti M, Deghenghi R, Ghigo E 2002 Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity. Eur J Pharmacol 440:235–254[CrossRef][Medline]
  5. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A, Doi K, Hosoda H, Kojima M, Kangawa K, Nakao K 2001 Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 86:4753–4758[Abstract/Free Full Text]
  6. Tolle V, Bassant MH, Zizzari P, Poindessous-Jazat F, Tomasetto C, Epelbaum J, Bluet-Pajot MT 2002 Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep-wake patterns in rats. Endocrinology 143:1353–1361[Abstract/Free Full Text]
  7. Sugino T, Hasegawa Y, Kikkawa Y, Yamaura J, Yamagishi M, Kurose Y, Kojima M, Kangawa K, Terashima Y 2002 A transient ghrelin surge occurs just before feeding in a scheduled meal-fed sheep. Biochem Biophys Res Commun 295:255–260[CrossRef][Medline]
  8. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS 2001 A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50:1714–1719[Abstract/Free Full Text]
  9. Tschop M, Wawarta R, Riepl RL, Friedrich S, Bidlingmaier M, Landgraf R, Folwaczny C 2001 Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest 24:19–21
  10. Strubbe JH 1992 Parasympathetic involvement in rapid meal-associated conditioned insulin secretion in the rat. Am J Physiol 263:R615–R618
  11. Mattes RD 1996 Oral fat exposure alters postprandial lipid metabolism in humans. Am J Clin Nutr 63:911–917[Abstract/Free Full Text]
  12. Ramirez I 1985 Oral stimulation alters digestion of intragastric oil meals in rats. Am J Physiol 248:R459–R463
  13. Erdmann J, Lippl F, Schusdziarra V 2003 Differential effect of protein and fat on plasma ghrelin levels in man. Regul Pept 116:101–107[CrossRef][Medline]
  14. Robertson MD, Jackson KG, Williams CM, Fielding BA, Frayn KM 2001 Prolonged effects of modified sham feeding on energy substrate mobilization. Am J Clin Nutr 73:111–117[Abstract/Free Full Text]
  15. Schwartz TW 1983 Pancreatic polypeptide: a hormone under vagal control. Gastroenterology 85:1411–1425[Medline]
  16. Nedvidkova J, Krykorkova I, Bartak V, Papezova H, Gold PW, Alesci S, Pacak K 2003 Loss of meal-induced decrease in plasma ghrelin levels in patients with anorexia nervosa. J Clin Endocrinol Metab 88:1678–1682[Abstract]
  17. Heath RB, Jones R, Frayn KN, Robertson MD 2004 Vagal stimulation exaggerates the inhibitory ghrelin response to oral fat in humans. J Endocrinol 180:273–281[Abstract]
  18. Taylor IL, Feldman M 1982 Effect of cephalic-vagal stimulation on insulin, gastric inhibitory polypeptide, and pancreatic polypeptide release in humans. J Clin Endocrinol Metab 55:1114–1117[Abstract]
  19. Chang HY, Mashimo H, Goyal RK 2003 Musings on the wanderer: what’s new in our understanding of vago-vagal reflex? IV. Current concepts of vagal efferent projections to the gut. Am J Physiol 284:G357–G366
  20. Murakami N, Hayashida T, Kuroiwa T, Nakahara K, Ida T, Mondal MS, Nakazato M, Kojima M, Kangawa K 2002 Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats. J Endocrinol 174:283–288[Abstract]
  21. Lee H-M, Wang G, Englander EW, Kojima M, Greeley GH 2002 Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 143:185–190[Abstract/Free Full Text]
  22. Williams DL, Grill HJ, Cummings DE, Kaplan JM 2003 Vagotomy dissociates short and long-term controls of circulating ghrelin. Endocrinology 144:5184–5187[Abstract/Free Full Text]
  23. Sugino T, Yamaura J, Yamagishi M, Kurose Y, Kojima M, Kangawa K, Hasegawa Y, Terashima Y 2003 Involvement of cholinergic neurons in the regulation of the ghrelin secretory response to feeding in sheep. Biochem Biophys Res Commun 304:308–312[CrossRef][Medline]
  24. Broglio F, Gottero C, van Koetsveld P, Prodam F, Destefanis S, Benso A, Gauna C, Hofland L, Arvat E, van der Lely AJ, Ghigo E 2004 Acetylcholine regulates ghrelin secretion in humans. J Clin Endocrinol Metab 89:2429–2433[Abstract/Free Full Text]
  25. Williams DL, Cummings DE, Grill HJ, Kaplan JM 2003 Meal-related ghrelin suppression requires postgastric feedback. Endocrinology 144:2765–2767[Abstract/Free Full Text]
  26. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S 2002 Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87:240–244[Abstract/Free Full Text]
  27. Monteleone P, Bencivenga R, Longobardi N, Serritella C, Maj M 2003 Differential responses of circulating ghrelin to high-fat or high-carbohydrate meal in healthy women. J Clin Endocrinol Metab 88:5510–5514[Abstract/Free Full Text]
  28. Briatore L, Andraghetti G, Cordera R 2003 Acute plasma glucose increase, but not early insulin response, regulates plasma ghrelin. Eur J Endocrinol 149:403–406[Abstract]
  29. Nakagawa E, Nagaya N, Okumura H, Enomoto M, Oya H, Ono F, Hosoda H, Kojima M, Kangawa K 2002 Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose. Clin Sci (Lond) 103:325–328[Medline]
  30. Cappiello V, Ronchi C, Morpurgo PS, Epaminonda P, Arosio M, Beck-Peccoz P, Spada A 2002 Circulating ghrelin levels in basal conditions and during glucose tolerance test in acromegalic patients. Eur J Endocrinol 147:189–194[Abstract]
  31. Lucidi P, Murdolo G, Di Loreto C, De Cicco A, Parlanti N, Fanelli C, Santeusanio F, Bolli GB, De Feo P 2002 Ghrelin is not necessary for adequate hormonal counterregulation of insulin-induced hypoglycemia. Diabetes 2002 51:2911–2914[Abstract/Free Full Text]
  32. Flanagan DE, Evans ML, Monsod TP, Rife F, Heptulla RA, Tamborlane WV, Sherwin RS 2003 The influence of insulin on circulating ghrelin. Am J Physiol Endocrinol Metab 284:E313–E316
  33. Caixas A, Bashore C, Nash W, Pi-Sunyer F, Laferrere B 2002 Insulin, unlike food intake, does not suppress ghrelin in human subjects. J Clin Endocrinol Metab 87:1902–1906[Abstract/Free Full Text]
  34. Schaller G, Schmidt A, Pleiner J, Woloszczuk W, Wolzt M, Luger A 2003 Plasma ghrelin concentrations are not regulated by glucose or insulin: a double-blind, placebo-controlled crossover clamp study. Diabetes 52:16–20[Abstract/Free Full Text]
  35. Broglio F, Koetsveld Pv P, Benso A, Gottero C, Prodam F, Papotti M, Muccioli G, Gauna C, Hofland L, Deghenghi R, Arvat E, Van Der Lely AJ, Ghigo E 2002 Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans. J Clin Endocrinol Metab 87:4829–4832[Abstract]
  36. Shimada M, Date Y, Mondal MS, Toshinai K, Shimbara T, Fukunaga K, Murakami N, Miyazato M, Kangawa K, Yoshimatsu H, Matsuo H, Nakazato M 2003 Somatostatin suppresses ghrelin secretion from the rat stomach. Biochem Biophys Res Commun 302:520–525[CrossRef][Medline]
  37. Haqq AM, Stadler DD, Rosenfeld RG, Pratt KL, Weigle DS, Frayo RS, LaFranchi SH, Cummings DE, Purnell JQ 2003 Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi syndrome. J Clin Endocrinol Metab 88:3573–3576[Abstract/Free Full Text]
  38. Saper CB, Chou TC, Elmquist JK 2002 The need to feed: homeostatic and hedonic control of eating. Neuron 36:199–211[CrossRef][Medline]
  39. Woods SC 1991 The eating paradox: how we tolerate food. Psychol Rev 98:488–505[CrossRef][Medline]
  40. Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A, Matsuo H, Kangawa K, Nakazato M 2002 The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 123:1120–1128[CrossRef][Medline]
  41. Chan JL, Bullen J, Lee JH, Yiannakouris N, Mantzoros CS 2004 Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects. J Clin Endocrinol Metab 89:335–343[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
M. Perez-Fontan, F. Cordido, A. Rodriguez-Carmona, M. Penin, H. Diaz-Cambre, A. Lopez-Muniz, S. Sangiao-Alvarellos, and J. Garcia-Buela
Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure
Nephrol. Dial. Transplant., May 23, 2008; (2008) gfn297v1.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. M. Frecka and R. D. Mattes
Possible entrainment of ghrelin to habitual meal patterns in humans
Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G699 - G707.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. Arnold, A. Mura, W. Langhans, and N. Geary
Gut Vagal Afferents Are Not Necessary for the Eating-Stimulatory Effect of Intraperitoneally Injected Ghrelin in the Rat
J. Neurosci., October 25, 2006; 26(43): 11052 - 11060.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Romon, S. Gomila, P. Hincker, B. Soudan, and J. Dallongeville
Influence of Weight Loss on Plasma Ghrelin Responses to High-Fat and High-Carbohydrate Test Meals in Obese Women
J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1034 - 1041.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
C. Maffeis, R. C Bonadonna, A. Consolaro, R. Vettor, C. Banzato, D. Silvagni, G. Bogoni, M. Pellegrino, and L. Tato
Ghrelin, insulin sensitivity and postprandial glucose disposal in overweight and obese children
Eur. J. Endocrinol., January 1, 2006; 154(1): 61 - 68.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. Teff
Learning Hunger: Conditioned Anticipatory Ghrelin Responses in Energy Homeostasis
Endocrinology, January 1, 2006; 147(1): 20 - 22.
[Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
J. Calissendorff, O. Danielsson, K. Brismar, and S. Rojdmark
Inhibitory effect of alcohol on ghrelin secretion in normal man
Eur. J. Endocrinol., May 1, 2005; 152(5): 743 - 747.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arosio, M.
Right arrow Articles by Peracchi, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arosio, M.
Right arrow Articles by Peracchi, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals