Marked Suppression of Ghrelin Concentration by Insulin in Prader-Willi Syndrome

The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86+/-0.15 to 0.58+/-0.12 ng/mL in the controls, and from 2.38+/-0.76 to 1.12+/-0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82+/-44.4 vs. -10.41+/-2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS.

Peptide YY, Cholecystokinin, Insulin and Ghrelin Response to Meal did not Change, but Mean Serum Levels of Insulin is Reduced in Children with Prader-Willi Syndrome

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.

Polymorphism of the Helicobacter pylori feoB Gene and Clinical Correlation with Iron-deficiency Anemia in Korea / 대한소아소화기영양학회지

PURPOSE: Helicobacter pylori infection is thought to be correlated with iron-deficiency anemia (IDA) at puberty. The H. pylori feoB gene, a high-affinity ferrous iron transporter, plays a central role in iron acquisition. This study aims to analyze the H. pylori feoB status according to the presence of antral gastritis with or without IDA. METHODS: Fourteen H. pylori-positive patients aged from 10~18 years were categorized into subgroups based on the presence or absence of IDA. Eight patients had IDA, and the other six showed normal hematological findings. Genomic DNA was isolated from cultured H. pylori. Five sets of primers were used for PCR amplification of the feoB gene. The feoB region, 1.93 kb, was generated by linking of the PCR products and sequenced. The feoB gene sequences of H. pylori J99 and 26695 were used to compare with the clinical strains. Sequence comparisons of the feoB regions between the IDA (+) and (-) groups were performed. RESULTS: Sequence analysis of the complete coding region of the feoB revealed 16 sites of polymorphism. Among these, 3 polymorphisms-Glu/Thr254Ala, Ile263Val, and Lys511Gln - were indigenous to Korean strains. Although statistically significant differences appear in 4 sites between IDA (+) and (-), the number of specimens are too low to assess the real differences. CONCLUSION: The 4 polymorphisms in the feoB gene seem to be related with IDA, but it is unclear yet because of small number of study strains. Further studies are required to prove the correlation of IDA and H. pylori infection.