Ghrelin drives GH secretion during fasting in man

Background: Helicobacter pylori, and the chronic gastric inflammation that it causes, may compromise the function and survival of ghrelin-producing cells, resulting in a decrease of circulating ghrelin levels. This finding raises the possibility that the infection might affect growth in children by reducing the ghrelin production. Aims: To determine baseline circulating levels of ghrelin and leptin in prepubertal children with and without H. pylori infection and to evaluate the long-term effects of H. pylori eradication on circulating levels of ghrelin and leptin as well as on body composition. Patients: Thirty children with H. pylori-associated gastritis, 35 children with H. pylori-negative gastric mucosa, and 20 healthy controls were studied. Results: At baseline, while leptin levels were significantly lower in H. pylori-positive patients, ghrelin concentrations did not differ among the three study groups. However, a significant inverse correlation between ghrelin concentrations and histological severity of gastritis was found. Eradication of the organism was associated with a progressive decrease in ghrelin concentrations over baseline at both 6-and 12-month follow-ups. SDS-body mass index (BMI), lean and fat mass, as well as leptin concentrations, significantly increased over baseline at both follow-ups. Conclusions: In prepubertal children, serum ghrelin concentrations are inversely related to the severity of H. pylori-associated gastritis. In these youngsters, long-term eradication of H. pylori infection is associated with a significant increase in BMI, lean and fat mass along with a significant decrease in circulating ghrelin levels and an increase in leptin levels.

Section: Discussioncontrasting

confidence: 74%

Long-term effects of Helicobacter pylori eradication on circulating ghrelin and leptin concentrations and body composition in prepubertal children

Pacifico¹,

Anania²,

Osborn³

et al. 2008

“…Insulin has been shown to downregulate IGFBP-1 synthesis and, probably for this reason, IGFBP-1 levels are altered in different nutritional states (34). These acute and long-term states of malnutrition are also characterised by elevated ghrelin levels (18,28). These findings together with our results raise a question: is it possible that ghrelin levels might play a role in the regulation of IGFBP-1 levels?…”

Section: Discussionsupporting

confidence: 60%

Sequencing analysis of the ghrelin receptor (growth hormone secretagogue receptor type 1a) gene

Vartiainen

Poykko²,

Raisanen³

et al. 2004

Objectives and design: Ghrelin is a novel 28 amino acid peptide which is reported to have several endocrine and non-endocrine actions. It possesses strong growth hormone (GH)-releasing activity, which is mediated via the GH secretagogue receptor type 1a (GHS-R1a). We hypothesised that there might be functional sequential variations in the GHS-R1a gene affecting phenotypes linked to the GH/insulin-like growth factor-I (IGF-I)-axis. Methods: To test our hypothesis we chose patients from our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study with low (n ¼ 96) and high (n ¼ 96) IGF-I levels, sequenced their GHS-R1a gene exons and performed association studies. Results: We found five single-nucleotide polymorphisms (SNPs) which did not change the amino acid sequence. We were unable to detect associations between the SNPs and the IGF-I plasma concentrations, but instead we showed that SNP 171C . T was associated with the values of the area under the insulin curve (AUCIN) in an oral glucose tolerance test and with IGF-binding protein-1 (IGFBP-1) concentrations (P , 0.05). SNP 477G . A was associated with the low density lipoprotein and very low density lipoprotein cholesterol plasma levels and AUCIN values (P , 0.05). Conclusions: This study was the first genomic screening of the GHS-R1a gene in a population. It suggests that genetic variations in the GHS-R1a gene are not the main regulators of IGF-I levels. However, the variants may be associated with IGFBP-1 concentrations and insulin metabolism.

“…Accordingly, in GH-deficient patients, systemic ghrelin levels were reported to be similar to those found in controls and not modified by GH replacement therapy (17). However, the recent demonstration that changes in ghrelin levels followed by similar changes in serum GH concentrations occur in normal subjects only during prolonged fasting may account for the lack of a significant correlation between GH and ghrelin levels in this still limited series of acromegalic patients who were tested after a standard overnight fast (28).…”

Section: Discussionmentioning

confidence: 89%

Circulating ghrelin levels in basal conditions and during glucose tolerance test in acromegalic patients

Cappiello¹,

Ronchi²,

Morpurgo³

et al. 2002

Background: Ghrelin exerts a wide range of metabolic functions. In contrast to the body of information accumulated on the role of ghrelin on energy balance, the possible relevance of the peptide on GH secretion in physiological and pathological conditions has so far been poorly investigated. Aim: The aim of the present study was to evaluate circulating ghrelin levels in acromegalic patients in basal conditions and in response to oral glucose tolerance test (OGTT). Patients: Serum ghrelin, insulin and leptin levels were measured in 31 healthy normal weight subjects as controls, 25 patients with simple obesity and 17 non-diabetic acromegalic patients. Ghrelin and insulin response to OGTT was evaluated in six controls, four obese and six acromegalic patients. Results: The acromegalic patients showed ghrelin levels lower than those observed in normal weight subjects (201^20 vs 329^32 pmol=l; P , 0:05) and similar to those found in obese subjects (165^14 pmol=l; P ¼ not significant). Both obese and acromegalic patients had insulin levels significantly higher than controls, while high levels of leptin were detected only in obese subjects. Serum ghrelin levels showed a significant negative correlation with insulin, leptin and body mass index ðP , 0:05Þ in normal and obese subjects. No correlation was observed in acromegalic patients, although those with severe insulin resistance showed the lowest ghrelin values ð161^20 pmol=lÞ: In controls and obese subjects, ghrelin levels showed a significant decrease (25 -40%) during OGTT, while no effect was detectable in acromegalic patients. Conclusions: This study reports that patients with active acromegaly show low levels of circulating ghrelin that are not further reduced by OGTT, this pattern of secretion probably depending on both GH-induced insulin resistance and the putative GH/IGF-I negative feedback control on ghrelin secretion.