通过胰岛素受体传递胰岛素信号,通过对骨和GH-IGF-1轴的影响增加线性生长
Marinna C Okawa1, Rebecca M Tuska1, Marissa Lightbourne1
1National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
The Journal of clinical endocrinology and metabolism
|August 18, 2023
概括
胰岛素受体 (InsR) 信号影响儿童生长和骨矿物质密度 (BMD). 损坏的InsR功能会减少生长和骨质量,而增加的InsR信号会加速它们.
科学领域:
- 内分泌学 在内分泌学.
- 儿科内分泌学 儿科内分泌学
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 儿童过度营养与增长和骨矿物质密度 (BMD) 的增加相关,而营养不良则显示相反的效果.
- 胰岛素受体 (InsR) 信号在这些生长和BMD表型中的确切作用仍然不完全理解.
- 罕见的遗传疾病为研究InsR信号提供了模型:先天性泛化脂质变 (CGL) 导致信号减少,高胰岛素性疾病 (INSR变体,B型胰岛素抵抗 (TBIR)) 导致信号增加.
研究的目的:
- 阐明InsR信号影响儿童生长和骨矿物质密度的机制.
- 为了比较具有不同的InsR信号状态的患者的生长和BMD参数.
主要方法:
- 在美国国立卫生研究院进行了一项横截面研究,比较了四组:CGL (N=23),INSR-/- (N=13),INSR+/- (N=17) 和TBIR (N=8).
- 关键的结果指标包括身高标准偏差 (SDS),体重指数 (BMI),胰岛素样生长因子-1 (IGF-1) 和BMD.
- 还评估了IGF结合蛋白 (IGFBP) -1和-3的水平.
主要成果:
- 与CGL患者相比,INSR-/-患者的胰岛素和IGFBP-1显著增加,但BMI SDS,身高 SDS,BMD SDS和IGFBP-3相比较低 (所有患者P < .05).
- 患者的INSR+/-结果是可变的.
- 在TBIR患者中,高胰岛素血症的缓解导致胰岛素和IGFBP-1的正常化,以及IGF-1和IGFBP-3的增加 (P < .05).
结论:
- 患有InsR功能受损和高胰岛素血症的患者表现出生长和 BMD 减弱,而高InsR信号传导 (CGL) 患者表现出加速生长和更高的 BMD.
- 这些发现表明,通过InsR的胰岛素作用直接影响骨代谢,并间接影响生长激素 (GH) -IGF-1轴.
- 在恢复InsR信号时,TBIR患者的GH轴异常的解决支持InsR活动和GH轴调节之间的因果关系.
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