Department of Internal Medicine, Division of Geriatrics Research, School of Medicine, Southern Illinois University, 801 N Rutledge, Room 4389, P.O. Box 19628, Springfield, IL 62794-9628, USA.
Biol Chem. 2010 Oct;391(10):1149-55. doi: 10.1515/BC.2010.124.
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 over- expression 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.
与生长激素（GH）对肌肉、骨骼和器官发育的刺激作用以及脂肪分解作用相反，它拮抗胰岛素对葡萄糖代谢的作用。人们认为，慢性 GH 过度暴露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 GH 过多或缺乏的人类状况都很重要，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。我们报告称，雄性和雌性成年 GH 转基因小鼠与同窝对照相比具有增强的葡萄糖耐量，并且这种作用不依赖于年龄或使用的特定异源 GH 转基因。此外，在牛 GH 过表达小鼠中还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糖异生减弱。这些结果表明，GH 转基因小鼠中明显增加的系统性 GH 浓度对葡萄糖稳态产生了意想不到的有益影响，可能是通过代偿性增加胰岛素释放。这些结果与以前对这些小鼠和其他 GH 过表达或抑制状态的生理学假设相矛盾。此外，它们提出了关于 GH、代谢的内分泌控制和衰老之间关系的有趣问题。
