Al-Regaiey Khalid A, Masternak Michal M, Bonkowski Michael S, Panici Jacob A, Kopchick John J, Bartke Andrzej
Departments of Internal Medicine, Southern Illinois University, School of Medicine, Springfield, USA.
J Gerontol A Biol Sci Med Sci. 2007 Jan;62(1):18-26. doi: 10.1093/gerona/62.1.18.
Growth hormone receptor-deficient (GHRKO) mice are long-lived and have reduced insulin-like growth factor (IGF)-1 and insulin levels and enhanced insulin sensitivity thus resembling the phenotype of animals subjected to calorie restriction (CR). In contrast to its effects in normal mice, CR does not improve insulin sensitivity or increase longevity in GHRKO males. In an attempt to identify mechanisms underlying this differential response to CR, effects of CR on the expression of insulin-related genes were compared in GHRKO and normal mice. In addition to changes detected in both genotypes, and responses unique to GHRKO mice, the levels of Akt2 and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1alpha) were increased and levels of phosphorylated c-Jun N-terminal kinase (JNK)1 were reduced in response to CR only in normal mice. These changes may be related to mechanisms of improving insulin sensitivity and life expectancy.
生长激素受体缺陷（GHRKO）小鼠寿命较长，胰岛素样生长因子（IGF）-1和胰岛素水平降低，胰岛素敏感性增强，因此类似于接受卡路里限制（CR）的动物的表型。与对正常小鼠的影响相反，CR并不能改善GHRKO雄性小鼠的胰岛素敏感性或延长其寿命。为了确定对CR这种差异反应的潜在机制，比较了CR对GHRKO小鼠和正常小鼠胰岛素相关基因表达的影响。除了在两种基因型中都检测到的变化以及GHRKO小鼠特有的反应外，仅在正常小鼠中，Akt2和过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC1α）的水平因CR而升高，磷酸化的c-Jun氨基末端激酶（JNK）1的水平降低。这些变化可能与改善胰岛素敏感性和预期寿命的机制有关。
