Effects of Growth Hormone and Thyroxine Replacement Therapy on Insulin Signaling in Ames Dwarf Mice
Effects of Growth Hormone and Thyroxine Replacement Therapy on Insulin Signaling in Ames Dwarf Mice
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DOI：
10.1093/gerona/glq018
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发表时间：
2010-04-01
影响因子：
5.1
通讯作者：
Masternak, Michal M.
中科院分区：
文献类型：
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作者：
Louis, Audreen;Bartke, Andrzej;Masternak, Michal M.
艾姆斯侏儒（Prop/（df），df/df）小鼠缺乏生长激素（GH），催乳素和促甲状腺激素，寿命明显长于其正常同胞。生长激素和甲状腺轴在发育和成年期的活动减少对寿命的意义尚不清楚。由于增强胰岛素敏感性和降低胰岛素水平是可能的机制，负责增加寿命在这些突变体中，我们比较了OH和甲状腺素（T4）替代对各种参数的影响，在年轻和年老的雄性DF/DF小鼠胰岛素信号。结果表明，血浆脂联素和胰岛素样生长因子-1（IGF-1）以及肝脏IGF-1、胰岛素受体（IR）、IR底物-1的改变。过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）γ和过氧化物酶体增殖物激活受体γ共激活因子-1 α可能导致艾姆斯侏儒胰岛素敏感性增加。GH和T4处理对血浆胰岛素的刺激作用和对肝脏葡萄糖转运蛋白-2表达的抑制作用在老年侏儒中大于年轻侏儒。这些结果表明，GH和T4治疗对发育和成年期的胰岛素信号传导具有不同的影响。
Ames dwarf (Prop/(df), df/df) mice lack growth hormone (GH), prolactin, and thyrotropin and live remarkably longer than their normal siblings. Significance of reduced activity of the somatotropic and thyroid axes during development and adulthood on longevity are unknown. Because enhanced insulin sensitivity and reduced insulin levels are among likely mechanisms responsible for increased longevity in these mutants, we compared the effects of OH and thyroxine (T4) replacement on various parameters related to insulin signaling in young and old male df/df mice. The results suggest that altered plasma adiponectin and insulin-like growth factor-1 (IGF-1) and hepatic IGF-1, insulin receptor (IR), IR substrate-1. peroxisome proliferator activated receptor (PPAR) gamma, and PPAR gamma coactivator-1 alpha may contribute to increased insulin sensitivity in Ames dwarfs. The stimulatory effect of GH and T4 treatment on plasma insulin and inhibitory effect on expression of hepatic glucose transporter-2 were greater in old than in young dwarfs. These results indicate that GH and T4 treatment has differential impact on insulin signaling during development and adulthood.