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胰岛素对生长激素的分泌和细胞内信号传导的影响

邱涵¹, 杨金奎², 陈晨^3,*

¹中山大学中山医学院法医学系，广州 510080；²首都医科大学同仁医院内分泌科，北京 100730；³昆士兰大学生物医学科学学院，布里斯班，Qld 4072，澳大利亚

摘要

生长激素(growth hormone, GH)在行使其功能时需要经历一系列的过程，包括从垂体分泌和进入血液循环到达靶器官或细胞(受体前过程)以及和生长激素受体(GH receptor, GHR)结合并引发细胞内信号转导(受体后过程)。胰岛素可以直接或间接地影响这些过程。GH从垂体的生长激素分泌细胞中分泌需要依赖于下丘脑释放的生长激素释放激素(GH-releasing hormone, GHRH)和生长激素抑制素(somatostatin, SS)，在生理或病理条件下，胰岛素可以对这两种激素以及GH分泌细胞施加不同影响，从而干预GH的分泌及循环水平。血糖、血脂以及饮食习惯都可以改变胰岛素对GH的影响。胰岛素还能通过影响GHR的敏感性，以及影响胰岛素样生长因子-1 (insulin-like growth factor 1, IGF-1)，进而影响GH。受体后过程也是GH行使功能的重要一环，细胞内信号转导依赖于信号通路完成。GH信号转导通路和胰岛素的信号通路有部分交叉，这使得两者的信号可以相互作用，胰岛素通过这种作用对GH的信号转导产生影响。还有很多因素可以改变胰岛素对GH的影响，包括细胞因子信号抑制物、GHR敏感性以及JAK2蛋白和胰岛素受体底物间的相互作用，且随着胰岛素浓度升高和作用时间延长，胰岛素对GH的影响趋向于增强。但胰岛素的浓度和时间对GH分泌和细胞内信号转导的具体影响还未完全阐明。胰岛素和SS的关系也有待进一步研究。

关键词： 胰岛素; 生长激素 ; 生长激素抑制素 ; 肥胖 ; 糖尿病 ; 信号转导通路

分类号：R587.1

Influence of insulin on growth hormone secretion, level and growth hormone signalling

QIU Han¹, YANG Jin-Kui², Chen Chen^3,*

¹Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China；²Endocrinology Department, Tongren Hospital, Capital Medical University, Beijing 100730, China；³School of Biomedical Science, University of Queensland, Brisbane, Qld 4072, Australia

Abstract

Growth hormone (GH), as a vital hormone, has to experience a series of processes to fulfill its function including secretion, entering the circulation to reach target tissues (pre-receptor process), binding on the GH receptor (GHR) and triggering signaling inside cells (post-GHR process). Insulin can directly or indirectly influence part of these processes. GH secretion from pituitary somatotropes is regulated by GH-releasing hormone (GHRH) and somatostatin (SS) from hypothalamus. Insulin may exert positive or negative effects on the neurons expressing GHRH and SS and somatotropes under healthy and pathological conditions including obesity and diabetes. Glucose and lipid levels in circulation and dietary habits may influence the effect of insulin on GH secretion. Insulin may also affect GHR sensitivity and the level of insulin-like growth factor 1 (IGF-1), thus influence the level of GH. The GH signaling is also important for GH to play its role. GH signaling involves GHR/JAK2/STATs, GHR/JAK2/SHC/MAPK and GH/ insulin receptor substrate (IRS)/PI3K/Akt pathways. These pathways may be shared by insulin, which is the basis for the interaction between insulin and GH, and insulin may attenuate or facilitate the GH signal by influencing molecules in the pathways. Many factors are related to the effect of insulin, among them the most important ones are duration of action and amount of insulin. The tendency of insulin-reduced GH signaling becomes obvious with increased dose and acting time of insulin. The participation of suppressor of cytokine signaling (SOCS), the interaction between JAK2 and IRS, and GHR sensitivity should also be considered when discovering GH signal. The involvement of SS in response to insulin is not clear yet. The details of how GH secretion, level and signaling change in response to time and dose of insulin treatment warrant further studies.

Key words: Insulin; growth hormone ; somatostatin ; obesity ; diabetes ; signal pathway

收稿日期：2017-02-20　　录用日期：2017-06-10

通讯作者：陈晨　　E-mail: chen.chen@uq.edu.au

DOI: 10.13294/j.aps.2017.0062

引用本文：

邱涵, 杨金奎, 陈晨. 胰岛素对生长激素的分泌和细胞内信号传导的影响[J]. 生理学报 2017; 69 (5): 541-556.

QIU Han, YANG Jin-Kui, Chen Chen. Influence of insulin on growth hormone secretion, level and growth hormone signalling. Acta Physiol Sin 2017; 69 (5): 541-556