Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis.
Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis.
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DOI：
10.1515/bc.2010.124
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发表时间：
2010-10
影响因子：
3.7
通讯作者：
Bartke A
中科院分区：
文献类型：
--
作者：
Boparai RK;Arum O;Khardori R;Bartke A
与其对肌肉组织、骨骼和器官发育的刺激作用及其脂解作用相反，生长激素（GH）对抗胰岛素对葡萄糖代谢的作用。慢性GH过度表达被认为会导致胰岛素不敏感和血糖稳态控制下降。然而，尽管这一概念对于基础生物学以及人类GH过量或缺乏的情况很重要，但尚未对GH过表达对葡萄糖稳态和胰岛素敏感性的影响进行系统评估。我们报告说，男性和女性成年GH转基因小鼠具有增强的葡萄糖耐量相比，同窝对照，这种效果是不依赖于年龄或特定的异源GH转基因使用。此外，在牛GH过表达小鼠中也观察到葡萄糖刺激的胰岛素分泌增加、胰岛素敏感性增强和沉默的胰岛素生成。这些结果表明，显着增加GH转基因小鼠的全身GH浓度发挥意想不到的有益作用，葡萄糖稳态，推测通过胰岛素释放的代偿性增加。这些结果的违反直觉的性质挑战了先前对这些小鼠的生理学和GH过表达或抑制的其他状态的假设。此外，他们对生长激素、代谢的内分泌控制和衰老之间的关系提出了有趣的问题。
In contrast to its stimulatory effects on musculature, bone, and organ development, and its lipolytic effects, growth hormone (GH) opposes insulin effects on glucose metabolism. Chronic GH overexposure is thought to result in insulin insensitivity and decreased blood glucose homeostatic control. Yet, despite the importance of this concept for basic biology, as well as human conditions of GH excess or deficiency, no systematic assessment of the impact of GH overexpression on glucose homeostasis and insulin sensitivity has been conducted. We report that male and female adult GH transgenic mice have enhanced glucose tolerance compared to littermate controls and this effect is not dependent on age or on the particular heterologous GH transgene used. Furthermore, increased glucose-stimulated insulin secretion, augmented insulin sensitivity, and muted gluconeogenesis were also observed in bovine GH overexpressing mice. These results show that markedly increased systemic GH concentration in GH-transgenic mice exerts unexpected beneficial effects on glucose homeostasis, presumably via a compensatory increase in insulin release. The counterintuitive nature of these results challenges previously held presumptions of the physiology of these mice and other states of GH overexpression or suppression. In addition, they pose intriguing queries about the relationships between GH, endocrine control of metabolism, and aging.