The consequences of growth hormone-releasing hormone receptor haploinsufficiency for bone quality and insulin resistance.
The consequences of growth hormone-releasing hormone receptor haploinsufficiency for bone quality and insulin resistance.
复制标题
DOI：
10.1111/j.1365-2265.2011.04263.x
复制
发表时间：
2012-09
影响因子：
3.2
通讯作者：
de Paula FJ
中科院分区：
文献类型：
--
作者：
Gois MB Jr;Salvatori R;Aguiar-Oliveira MH;Pereira FA;Oliveira CR;Oliveira-Neto LA;Pereira RM;Souza AH;Melo EV;de Paula FJ
生长激素（GH）/胰岛素样生长因子（IGF）轴和胰岛素是骨重建的关键决定因素。GH释放激素受体（GHRHR）基因（GHRHR）的纯合突变是遗传性孤立性GHD（IGHD）的常见原因。GHRHR突变的杂合性导致身体组成的变化，并可能增加胰岛素敏感性，但其对骨质量的影响仍然是未知的。本研究的目的是评估GHRHR无效突变杂合子受试者的骨质量和代谢及其与胰岛素敏感性的相关性。对76名正常受试者（68.4%女性）（N/N）和64名GHRHR突变杂合子个体（64.1%女性）（MUT/N）进行了横断面研究。测量人体测量特征、足跟定量超声（QUS）、骨标志物（骨钙素和CrossLaps）、IGF-I、葡萄糖和胰岛素，并计算胰岛素抵抗的稳态模型评估（HOMAIR）。两组之间的年龄或身高没有差异，但MUT/N组的体重（p = 0.007）和BMI（p = 0.001）较低。MUT/N组的血清IGF-I、血糖、T评分或僵硬度和骨钙素的绝对值无差异，但胰岛素（p = 0.01）、HOMAIR（p = 0.01）和CrossLaps（p = 0.01）较低。在140名个体中，无论是MUT/N组还是N/N组，骨钙素与血糖、骨钙素与HOMAIR均无相关性。目前的研究表明，GHRHR基因中的一个等位基因突变对能量代谢的影响大于对骨质量的影响。
Growth hormone (GH)/insulin like growth factor (IGF) axis and insulin are key determinants of bone remodeling. Homozygous mutations in the GH releasing hormone receptor (GHRHR) gene (GHRHR) are a frequent cause of genetic isolated GHD (IGHD). Heterozygosity for GHRHR mutation causes changes in body composition and possibly an increase in insulin sensitivity, but its effects on bone quality are still unknown. The objective of this study was to assess the bone quality and metabolism and its correlation with insulin sensitivity in subjects heterozygous for a null mutation in the GHRHR. A cross-sectional study was performed on 76 normal subjects (68.4% females) (N/N) and 64 individuals (64.1% females) heterozygous for a mutation in the GHRHR (MUT/N). Anthropometric features, quantitative ultrasound (QUS) of the heel, bone markers (osteocalcin and CrossLaps), IGF-I, glucose, and insulin were measured and homeostasis model assessment of insulin resistance (HOMAIR) was calculated. There were no differences in age or height between the two groups, but weight (p = 0.007) and BMI (p = 0.001) were lower in MUT/N. There were no differences in serum levels of IGF-I, glucose, T score, or absolute values of stiffness and osteocalcin, but insulin (p = 0.01), HOMAIR (p = 0.01) and CrossLaps (p = 0.01) were lower in MUT/N. There was no correlation between osteocalcin and glucose, osteocalcin and HOMAIR in the140 individuals as a whole or in the separate MUT/N or N/N groups. The present study suggests that one allele mutation in the GHRHR gene has a greater impact on energy metabolism than on bone quality.
登录
查看更多内容
影响因子：
4.2
作者：
de Paula, Francisco J. A.;Dick-de-Paula, Ingrid;Bornstein, Sheila;Rostama, Bahman;Le, Phuong;Lotinun, Sutada;Baron, Roland;Rosen, Clifford J.
通讯作者：
Rosen, Clifford J.
影响因子：
5.8
作者：
Salvatori, R;Hayashida, CY;Levine, MA
通讯作者：
Levine, MA
影响因子：
64.5
作者：
Lee, Na Kyung;Sowa, Hideaki;Karsenty, Gerard
通讯作者：
Karsenty, Gerard
影响因子：
5.8
作者：
Pittas, Anastassios G.;Harris, Susan S.;Dawson-Hughes, Bess
通讯作者：
Dawson-Hughes, Bess
影响因子：
4.2
作者：
Gillberg, P;Olofsson, H;Nilsson, AG
通讯作者：
Nilsson, AG