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Context: Ghrelin, a natural GH secretagogue, is mainly characterized by nonendocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated with insulin secretion, enhanced in anorexia, and reduced in obesity. Ghrelin levels in newborns were shown to be similar to those found in children and adults without any gender-related difference., Objective: The aim of this study was to evaluate ghrelin variations in preterm newborns as a function of fasting and feeding., Methods: To this end, in 31 preterm neonates (13 males and 18 females) categorized as appropriate for gestational age, total ghrelin levels were measured in cord blood and then on the fourth day of life before and after meals., Results: Ghrelin levels in cord blood [(median 25th-75th centile) 184; 122-275 pg/ml] were higher (P < 0.006) than levels measured in the mothers at delivery (167.0; 89-190 pg/ml). In newborns on the fourth day of life, ghrelin levels in fasting conditions (451; 348-649 pg/ml) were higher (P < 0.0004) than those in cord blood. The meal did not at all modify ghrelin levels (476; 302-775 pg/ml), which were unchanged, compared with those in fasting condition. Total ghrelin levels in cord blood were not associated with weight and length; conversely, on the fourth day of life ghrelin levels in newborns were negatively correlated to birth weight as well as the present weight (P = 0.05, r = -0.4). Ghrelin levels were independent of gender, type of delivery, and the kind of feeding regimen., Conclusions: The secretion of total ghrelin increases from delivery to the fourth day of life when it is refractory to the inhibitory effect of food intake, but it is negatively correlated to body weight.

Objective: The presence of both the GH secretagogue (GHS) receptor and ghrelin in the pancreas indicates an involvement of this hormone in glucose metabolism. Ghrelin secretion is increased by fasting and energy restriction, decreased by food intake, glucose load, insulin and somatostatin in normal adults; however, food intake is not able to inhibit circulating ghrelin levels in children, suggesting that the profile of ghrelin secretion in children is different from that in adults. Moreover, how ghrelin secretion is regulated in childhood as a function of fat mass is still unclear., Design and Subjects: We studied the effect of oral glucose load (75 g solution orally) on circulating total ghrelin levels in 14 obese children (group A, four boys and 10 girls, aged 9.3 +/- 2.3 years) and 10 lean children (group B, five boys and five girls, aged 9.7 +/- 3.8 years)., Measurements: In all the sessions, blood samples were collected every 30 min from 0 up to +120 min. GH, insulin and glucose levels were assayed at each time point., Results: Glucose peaks following an oral glucose tolerance test (OGTT) in groups A and B were similar; however, both basal and OGTT-stimulated insulin levels in group A were higher than in group B (P < 0.05). Basal total ghrelin levels in group A (281.3 +/- 29.5 pg/ml) were lower (P < 0.0005) than in group B (563.4 +/- 81.5 pg/ml). In both groups A and B, the OGTT inhibited total ghrelin levels (P < 0.005). In terms of absolute values, total ghrelin levels in group A were lower (P < 0.0005) than those in group B at each time point after glucose load. The percentage nadir in total ghrelin levels recorded in group A (-25% at 90 min) was similar to that recorded in group B (-31% at 120 min). Total ghrelin levels were negatively associated with BMI (r = 0.5, P < 0.005) but not with glucose or insulin levels., Conclusion: Ghrelin secretion is reduced in obese children. It is, however, equally sensitive in both obese and lean children to the inhibitory effect of oral glucose load.

Objective: Circulating ghrelin levels are increased by fasting and decreased by feeding, glucose load, insulin and somatostatin. Whether hyperglycaemia and insulin directly inhibit ghrelin secretion still remains matter of debate. The aim of the present study was therefore to investigate further the regulatory effects of glucose and insulin on ghrelin secretion., Design and Subjects: We studied the effects of glucose [oral glucose tolerance test (OGTT) 100 g orally], insulin-induced hypoglycaemia [ITT, 0.1 IU/kg insulin intravenously (i.v.)], glucagon (1 mg i.v.), arginine (0.5 mg/kg i.v.) and saline on ghrelin, GH, insulin, glucose and glucagon levels in six normal subjects., Measurements: In all the sessions, blood samples were collected every 15 min from 0 up to + 120 min. Ghrelin, GH, insulin, glucagon and glucose levels were assayed at each time point., Results: OGTT increased (P < 0.01) glucose and insulin while decreasing (P < 0.01) GH and ghrelin levels. ITT increased (P < 0.01) GH but decreased (P < 0.01) ghrelin levels. Glucagon increased (P < 0.01) glucose and insulin without modifying GH and ghrelin. Arginine increased (P < 0.01) GH, insulin, glucagon and glucose (P < 0.05) but did not affect ghrelin secretion., Conclusions: Ghrelin secretion in humans is inhibited by OGTT-induced hyperglycaemia and ITT but not by glucagon and arginine, two substances able to increase insulin and glucose levels. These findings question the assumption that glucose and insulin directly regulate ghrelin secretion. On the other hand, ghrelin secretion is not associated with the GH response to ITT or arginine, indicating that the somatotroph response to these stimuli is unlikely to be mediated by ghrelin.

Background: Previous investigations on the ghrelin gene reported three common polymorphisms (Arg51Gln, Leu72Met, and Gln90Leu), but their role in overweight and obese individuals remains to be clarified., Objective: To ascertain whether these genetic variants could influence ghrelin secretion and play a part in predisposing to earlier onset of obesity or in modulating the overweight phenotype in childhood., Design and Methods: Mutational analysis of the entire ghrelin gene and total and acylated plasma determinations were performed in 81 obese or overweight children and adolescents (46 were obese and 35 overweight: Ob/Ow). We also recruited 168 normal-weight healthy controls (72 young adults and 96 children) for mutational or plasma ghrelin analysis., Results: Median total and acylated plasma ghrelin concentrations were significantly lower in Ob/Ow individuals than in controls (175 pg/ml compared with 345 pg/ml, P<0.0001, and 95 pg/ml compared with 114 pg/ml, P<0.0001, respectively). The ghrelin gene variants showed similar allele frequencies in the Ob/Ow individuals and in controls; in the former, they were not associated with any change in total and acylated circulating ghrelin concentrations or anthropometric data. The Leu72Met status was associated with a positive family history for obesity (75% for Leu72Met compared with 39% for Leu72Leu, P=0.03) and with a greater percentage of newborns born 'large for gestational age' (33% for Leu72Met compared with 5% for Leu72Leu, P=0.03), but in the control group it was related to a lower mean body mass index z-score (-0.03 for Leu72Met and -0.47 for Leu72Leu, P=0.04)., Conclusion: Our present findings do not support the hypothesis that the ghrelin gene polymorphisms have a relevant impact in the secretion of total and acylated ghrelin.

Objective: Ghrelin exerts potent GH-releasing activity and stimulates food intake. Circulating ghrelin levels are increased in anorexia and cachexia, reduced in obesity and restored by weight recovery. Newborns are characterized by GH hypersecretion associated with low IGF-I levels reflecting peripheral GH resistance., Study Design: The aim of our study was to measure cord ghrelin levels in 117 newborns appropriate for gestational age, born either at term or preterm., Results: Ghrelin levels in cord blood (median; 25th-75th centile: 327.6; 206.0-413.0 pg/ml) were higher (P < 0.0001) than those in maternal blood at delivery (133.0; 89.0-173.7 pg/ml), without gender differences. A positive correlation between ghrelin levels in mothers and newborns (r = 0.26, P < 0.01) was observed. Ghrelin levels in newborns born at term (399.0; 229.0-438.0 pg/ml) were remarkably higher (P < 0.0001) than those in born preterm (208.0; 144.5-278.9 pg/ml). A clear positive association was present between ghrelin levels and gestational age. No association between ghrelin and GH, IGF-I, insulin, glucose and leptin levels were found., Conclusions: Cord ghrelin levels show clear gestational age-related dependency. The lack of any direct relationship between ghrelin and anthropometric or biochemical parameters in adequate for gestational age newborns does not support the hypothesis that ghrelin has major role in foetal GH secretion and growth.

Ghrelin, a natural GH secretagogue, is predominantly produced by the stomach. Ghrelin has other actions including orexant activity, modulation of energy balance, and modulation of endocrine and nonendocrine functions. Ghrelin secretion is increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. Ghrelin secretion does not seem to be a function of age; in fact, morning ghrelin levels after overnight fasting in prepubertal and pubertal children are similar to those in young adults. To clarify whether children and adults have the same sensitivity to the inhibitory effect of food intake, we studied the ghrelin response to a standardized light breakfast (SLB) in 10 prepubertal lean children whose results were compared with those recorded in 19 normal-weight adults. Basal ghrelin levels in children (median, 224.5; 25th to 75th percentile, 122.0-447.7 pg/ml) and adults (338.0; 238.0-512.0 pg/ml) were similar. SLB inhibited ghrelin levels in adults (263.0; 190.0-399.0 pg/ml). However, no change in ghrelin levels after SLB (206.5; 105.0-274.0 pg/ml) was recorded in children. Thus, food intake inhibits ghrelin secretion in adults but not in children. Ghrelin refractoriness to inhibition by food intake in children would reflect a peculiar functional profile of the ghrelin system in childhood.

Ghrelin levels are increased by fasting and energy restriction, decreased by food intake, glucose load and insulin but not by lipids and amino acids. Accordingly, ghrelin levels are elevated in anorexia and cachexia and reduced in obesity. Herein we compared the effects of a standardized light breakfast (SLB) on morning circulating ghrelin levels with those of oral glucose load (OGTT) in normal subjects. Specifically, 8 young adult volunteers [age (mean+/-SEM): 28.0+/-2.0 yr; body mass index (BMI): 22.4+/-0.6 kg/m2] underwent the following testing sessions: a) OGTT (100 g p.o. at 0 min, about 400 kcal); b) SLB (about 400 kcal, 45% carbohydrates, 13% proteins and 42% lipids at 0 min) on three different days; c) placebo (100 ml water p.o.). In all sessions, at baseline, blood samples were withdrawn twice at 5-min interval to characterize the inter- and intra-individual reproducibility of the variables assayed. After placebo and OGTT, blood samples were withdrawn every 15 min up to +120 min. After SLB, blood samples were taken at 60 min only. Ghrelin, insulin and glucose levels were assayed at each time point in all sessions. Similarly to insulin and glucose levels, at baseline, ghrelin showed remarkable intra-subject reproducibility both in the same sessions and among the different sessions. Placebo did not significantly modify ghrelin, insulin and glucose. OGTT increased (p<0.01) glucose (baseline vs peak: 80.0+/-3.6 vs 140.5+/-6.3 mg/dl) and insulin (20.2+/-6.2 vs 115.3+/-10.3 mU/l) levels. SLB increased (p<0.05) both insulin (16.3+/-1.8 vs 48.3+/-6.3 mU/l) and glucose (74.5+/-3.7 vs 82.9+/-3.1 mg/dl) levels. Notably both the insulin and glucose increases after OGTT were significantly higher (p<0.01) than that induced by SLB. After OGTT, ghrelin levels underwent a significant reduction (baseline vs nadir: 355.7+/-150.8 vs 243.3+/-98.8 pg/ml; p<0.05) reaching the nadir at time +60 min. Similarly, ghrelin levels 60 min after SLB (264.8+/-44.8 pg/ml) were significantly (p<0.01) lower than at baseline (341.4+/-54.9 pg/ml). No significant differences in the reduction of ghrelin levels after OGTT and SLB were observed. In conclusion, these findings show that light breakfast inhibits ghrelin secretion to the same extent of OGTT in adults despite lower variations in glucose and insulin levels.

Ghrelin, a new gastric-derived hormone, probably plays a major role in managing energy balance and the neuroendocrine response to starvation. Information about the age-related variation in ghrelin secretion is scanty. We measured circulating ghrelin levels in 93 full term newborns adequate for gestational age, in 39 normal children and in 19 lean healthy adults. Our findings demonstrate that ghrelin levels are independent of age and gender from birth to adulthood. Interestingly, ghrelin secretion at birth is not associated to body weight and hormonal parameters such as GH, insulin and leptin levels. On the other hand, ghrelin levels seem dependent on the type of delivery, being lower in newborns after caesarean section with respect to those after normal delivery.

Ghrelin, a natural GH secretagogue, exerts remarkable endocrine and non-endocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated to insulin secretion, enhanced in anorexia and reduced in obesity. Ghrelin levels in childhood have never been evaluated. We measured morning ghrelin levels after overnight fasting in 29 healthy lean children (NC) and in 36 obese children (OBC). The results were compared with those recorded twice in 3 different sessions in healthy lean adults (NA). In NA ghrelin levels showed good within-subject reproducibility without gender-related differences. Ghrelin levels in NC [(median; 25 degrees -75 degrees centile): 426.0; 183.0-618.0 pg/ml] were similar to those in NA (380.5; 257.7-551.7 pg/ml). Ghrelin levels in OBC (229.5; 162.5-339.5 pg/ml) were lower (p<0.03) than in NC (426.0; 183.0-618.0 pg/ml). Both in NC and in OBC, ghrelin levels were independent of gender and pubertal status. In all children, ghrelin levels were negatively associated (p<0.05) to weight excess (r=-0.24), insulin (r=-0.28) and IGF-I (r=-0.4) levels. In conclusion, these findings demonstrate that morning ghrelin levels after overnight fasting show good within-subject reproducibility, and are similar in both sexes and do not vary from childhood to adulthood. In childhood, circulating ghrelin levels are reduced in obese subjects being negatively correlated to overweight and insulin secretion.