Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, 801 N. Rutledge, Springfield, IL 62794-9628, USA.
J Gerontol A Biol Sci Med Sci. 2010 Jan;65(1):24-30. doi: 10.1093/gerona/glp172. Epub 2009 Nov 11.
The disruption of the growth hormone (GH) axis in mice promotes insulin sensitivity and is strongly correlated with extended longevity. Ames dwarf (Prop1(df), df/df) mice are GH, prolactin (PRL), and thyrotropin (TSH) deficient and live approximately 50% longer than their normal siblings. To investigate the effects of GH on insulin and GH signaling pathways, we subjected these dwarf mice to twice-daily GH injections (6 microg/g/d) starting at the age of 2 weeks and continuing for 6 weeks. This produced the expected activation of the GH signaling pathway and stimulated somatic growth of the Ames dwarf mice. However, concomitantly with increased growth and increased production of insulinlike growth factor-1, the GH treatment strongly inhibited the insulin signaling pathway by decreasing insulin sensitivity of the dwarf mice. This suggests that improving growth of these animals may negatively affect both their healthspan and longevity by causing insulin resistance.
生长激素（GH）轴的破坏会促进胰岛素敏感性，并与延长寿命强烈相关。Ames 矮小（Prop1(df)，df/df) 小鼠缺乏 GH、催乳素（PRL）和促甲状腺激素（TSH），比其正常兄弟姐妹长约 50%。为了研究 GH 对胰岛素和 GH 信号通路的影响，我们从 2 周龄开始每天两次给这些矮鼠注射 GH（6 μg/g/d），持续 6 周。这产生了预期的 GH 信号通路的激活，并刺激了 Ames 矮小鼠的体细胞生长。然而，与生长增加和胰岛素样生长因子-1 产量增加同时发生的是，GH 治疗通过降低矮小鼠的胰岛素敏感性强烈抑制了胰岛素信号通路。这表明，改善这些动物的生长可能会通过引起胰岛素抵抗而对它们的健康寿命和寿命产生负面影响。
