Ghrelin, the recently identified endogenous ligand of the GH secretagogue receptor, is a gut-brain peptide with endocrine, orexigenic, and gastrointestinal effects. In rodents it increases circulating gastrin and insulin levels, whereas in man it appears to decrease insulin secretion despite a rise in blood glucose levels. The aim of the present study was to evaluate the effects of ghrelin administration on total circulating somatostatin (SS), pancreatic polypeptide (PP), and gastrin levels compared with those elicited on insulin, glucose, and GH. Eight healthy volunteers of normal weight (four women and four men) were injected with 3.3 microg/kg ghrelin or saline after an overnight fast on 2 different days. Blood was taken every 15 min for 1 h and then every 30 min for 2 h. As expected, ghrelin injection elicited a prompt GH and glucose increase with a peak at 30 min and an insulin decrease with a nadir at 60 min. Gastrin concentrations were not modified, whereas significant rises were observed in both SS (in a biphasic pattern with peaks at 15 and 120 min) and PP (which increased promptly with a peak at 15 min). A significant negative correlation was found between SS (first peak) and insulin changes (r = -0.86; P < 0.01). In conclusion, this study clearly demonstrates that ghrelin stimulates SS and PP release in man. Although the underlying mechanisms and biological significance of these pharmacological effects remain to be elucidated, a causal relationship between the SS increase and the insulin changes may be hypothesized. Finally, these findings strongly support ghrelin's postulated role in linking the endocrine control of energy balance and growth with the regulation of gastrointestinal functions.
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/m(2)) 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.
Objective: In atrophic body gastritis (ABG) chronic hypergastrinaemia stimulates enterochromaffinlike (ECL) cell proliferation with development of cell hyperplasia, dysplasia and possibly type-1 gastric carcinoids. As circulating chromogranin A (CgA) levels are a marker of neuroendocrine tumours, we evaluated the clinical usefulness of CgA assay in ABG patients to detect those with carcinoids. Design and methods: Plasma CgA levels were measured using a commercial ELISA in 45 healthy volunteers, nine patients with type-1 gastric carcinoids and 43 consecutive ABG patients (21 without and 22 with ECL cell hyperplasia/dysplasia). Results: CgA levels were significantly higher in ABG patients with and without gastric carcinoids than in healthy subjects (P , 0.001). The highest values occurred in patients with carcinoids (median (interquartile range): 58.1 (44.5 -65.3) U/l) and with ECL cell hyperplasia/dysplasia (35.5 (31.8 -48.65) U/l) but there were no significant differences in CgA among the various subgroups of ABG patients classified according to ECL cell status. Nevertheless, in ABG patients without carcinoids CgA values correlated with the presence and severity of ECL cell lesions (r s ¼ 0.428, P , 0.01). The sensitivity and specificity of the CgA assay in identifying patients with carcinoids were 100 and 23% respectively. Conclusions: CgA plasma levels reflect the histological degree of ECL cell lesions in patients with ABG but the assay specificity is too low to detect among these patients those with gastric carcinoids. European Journal of Endocrinology 152 443-448
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.