A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children
A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children
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DOI：
10.1210/jc.87.8.4005
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发表时间：
2002-08-01
影响因子：
5.8
通讯作者：
Froguel, P
中科院分区：
文献类型：
--
作者：
Korbonits, M;Gueorguiev, M;Froguel, P
Ghrelin是新近发现的一种起源于胃粘膜的肠脑肽。它刺激生长激素释放，增加食欲，促进脂肪储存，并可能与葡萄糖代谢相互作用。我们研究了70名高个子和肥胖儿童(平均年龄9.4岁，Z体重指数[BMI]和Z身高和/或BMI百分位数99%)的Ghrelin基因。我们发现了10个单核苷酸多态。Ghrelin基因的一个常见多态，对应于Ghrelin前体分子尾部的氨基酸变化，与体重指数较高的儿童显著相关(P=0.001.0 5)，与口服葡萄糖耐量试验第一阶段胰岛素分泌减少(P=0.0 5)显著相关，尽管血糖水平没有差异。这可能表明胰岛素敏感性增加，尽管空腹和2小时胰岛素水平缺乏差异并不支持这一点；或者，这可能表明第一时相胰岛素分泌受损。这些数据表明，Ghrelin基因的变异导致儿童肥胖，并可能调节葡萄糖诱导的胰岛素分泌。
Ghrelin is a recently recognized gut-brain peptide originally derived from the gastric mucosa. It stimulates growth hormone release, increases appetite and facilitates fat storage, and may interact with glucose metabolism. We studied the ghrelin gene in a group of 70 tall and obese children (mean age 9.4 year, Z body mass index [BMI] and Z height >3 and/or BMI percentile >99%). We found 10 single nucleotide polymorphisms. One common polymorphism of the ghrelin gene, which corresponds to an amino acid change in the tail of the prepro-ghrelin molecule, was significantly associated with children with a higher BMI (P=0.001), and with lower insulin secretion during the first part of an oral glucose tolerance test (P=0.05) although no difference in glucose levels was noted. This might suggest increased insulin sensitivity, although this is not supported by the lack of difference in fasting and 2 hour insulin levels; alternatively, this may be indicative of impaired first phase insulin secretion. These data suggest that variations in the ghrelin gene contribute to obesity in children and may modulate glucose-induced insulin secretion.