Our results suggest that AG is sensitively suppressed by insulin and that this suppression correlated with insulin sensitivity in PWS children.

Our results indicate that plasma obestatin is not elevated in PWS children and is not regulated by insulin both in PWS children and in obese controls.

The lactoferrin sequestration in the gastric mucosa of HPIDA was remarkable, and this finding seems to give a clue that leads to the clarification of the mechanism by which H. pylori infection contributes to iron-deficiency anemia.

No abstract

Ghrelin is a GH-releasing acylated peptide found in the stomach and a centrally acting food intake stimulator. Prader-Willi syndrome (PWS) is a genetic disorder characterized by a voracious appetite and increased fasting ghrelin levels. In this report we describe 24-h ghrelin profiles in PWS children (n = 5) and compare these with age, sex, and body mass index (BMI)-matched controls (n = 5). A 3- to 4-fold increase in ghrelin levels was found in PWS over a 24-h period, compared with controls (P < 0.001). Interestingly, there was a greater tendency for the up-regulation of ghrelin level in lean PWS than in obese PWS. To confirm this finding, we measured fasting ghrelin levels in 39 patients with PWS. Inverse correlations were found between plasma ghrelin levels and the following: age (r = -0.408, P = 0.005), BMI (r = -0.341, P = 0.017), percentage of the ideal weight for age (r = -0.382, P = 0.008), and BMI percentile (r = -0.311, P = 0.027). Our data show that there may be a suppressive (or up-regulating) controlling mechanism of ghrelin secretion in obese (or lean) PWS children. We hope that our data may further explain the mechanisms underlying the insatiable appetite and obesity characteristic of PWS.

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.

Context:The levels of ghrelin, an orexigenic hormone secreted by oxyntic cells in the digestive tract, are elevated in Prader-Willi syndrome (PWS) and GH deficiency (GHD) patients. In this study, we hypothesized that the hyperghrelinemia observed in PWS is related to IGF-I or GH/IGF axis deficiency. Design:We investigated the densities of ghrelin-expressing cells (GECs), the amounts of ghrelin in gastric tissues, and ghrelin levels in plasma in 16 PWS patients and compared these results with those of 13 GHD patients and comparison groups (19 normal lean and 10 normal obese subjects). Results:In the gastric body and fundus, 2-to 3-fold increases in the numbers of GECs (P Ͻ 0.001) and in the amounts of ghrelin (P Ͻ 0.018) were noted in PWS patients vs. comparison groups, whereas GEC numbers in GHD patients were similar to those of the comparison group despite elevated fasting plasma ghrelin levels. In addition, IGF-I SD scores in PWS were not found to be correlated with GEC densities, the amounts of ghrelin expressed in gastric tissues, or plasma ghrelin levels. Conclusions:Our results suggest that IGF-I or GH/IGF axis deficiency appears to be unrelated to observed GEC increases in the stomach of patients with PWS. G HRELIN IS AN acylated peptide that is secreted byA-like endocrine cells of the oxyntic mucosa of the stomach and induces the secretion of GH (1, 2). Removing the acid-producing portion of the stomach was found previously to reduce circulating ghrelin by 80%, supporting the notion that the oxyntic mucosa is the major source of circulating ghrelin (3). Ghrelin can induce acute hunger, increase food intake, and reduce fat utilization in rodents and humans (1, 4). However, the direct orexigenic effect of ghrelin in its physiologic concentration range has not been elucidated in rodents or humans.Prader-Willi syndrome (PWS) is the most common form of human syndromic obesity. Ghrelin levels have been reported to be elevated in PWS (5-7). Moreover, unlike normal obese individuals, who have low fasting-plasma ghrelin concentrations, PWS patients can have 3-to 4-fold higher ghrelin fasting concentrations (5-7). Elevated plasma ghrelin levels in PWS may be related to low plasma insulin levels, because insulin plays an important role in the suppression of plasma ghrelin (8 -10).Recently, plasma ghrelin levels were reported to be elevated in patients with GH deficiency (GHD) (11,12). Because some PWS patients show attenuated plasma GH levels, and because total and free IGF-I have been reported to be low in PWS compared with obese individuals, partial GHD may also contribute to the hyperghrelinemia in PWS.In the present study, we hypothesized that the hyperghrelinemia observed in PWS is related to IGF-I or GH/IGF axis deficiency. We investigated plasma ghrelin levels, ghrelin-expressing cell (GEC) densities, and ghrelin quantities in the gastric tissues of PWS and GHD patients and in those of lean and obese normal subjects and correlated these results with total IGF-I levels. We found that GEC densities and ghreli...

Prader-Willi syndrome (PWS) is the most common form of syndromic obesity associated with hyperphagia. Because ghrelin stimulates gastric motility in rodents, and PWS patients have 3- to 4-fold higher fasting plasma ghrelin concentrations than normal subjects, we hypothesized that hyperphagia associated with PWS may be partly explained by rapid gastric emptying due to the increased gastric motility caused by ghrelin. We determined gastric emptying times (GETs) and measured ghrelin levels in 11 PWS children and 11 age-, sex-, and body mass index-matched controls using a standard meal containing [(99m)Tc]diaminetriaminepentacetate. Median plasma ghrelin levels before (precibum) and after the GET study were higher in PWS patients than in controls (P = 0.004 and P = 0.001, respectively). Median percent gastric retentions at 90 min after the standard meal were 57.1% (range, 34.0-83.2%) in PWS patients and 40.2% (range, 27.2-60.2%) in controls (P = 0.03). In particular, precibum ghrelin concentrations were not significantly correlated with the rate of gastric emptying in PWS patients (P = 0.153; r = 0.461) or controls (P = 0.911; r = 0.048). Our results show that gastric emptying in PWS is reduced despite higher ghrelin levels, and that the voracious appetite associated with PWS is related to another mechanism.