Metabolic impact of adult-onset, isolated, growth hormone deficiency (AOiGHD) due to destruction of pituitary somatotropes.
Metabolic impact of adult-onset, isolated, growth hormone deficiency (AOiGHD) due to destruction of pituitary somatotropes.
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DOI：
10.1371/journal.pone.0015767
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发表时间：
2011-01-19
期刊：
影响因子：
3.7
通讯作者：
Kineman RD
中科院分区：
文献类型：
--
作者：
Luque RM;Lin Q;Córdoba-Chacón J;Subbaiah PV;Buch T;Waisman A;Vankelecom H;Kineman RD
生长激素（GH）抑制脂肪积累并促进蛋白质增加，因此随着体重增加和正常衰老观察到的GH下降可能导致代谢功能障碍。为了直接验证这一假设，通过将大鼠GH启动子驱动的Cre重组酶小鼠（Cre）与诱导型白喉毒素受体小鼠（iDTR）杂交，并用DT处理成年Cre+/−、iDTR+/−后代以选择性破坏脑垂体前叶的生长激素细胞群，导致循环GH和IGF-I水平降低，从而产生了一种新的成人发作孤立性GH缺乏症（AOiGHD）小鼠模型。DT处理的Cre−/−、iDTR+/−小鼠用作GH完整对照。AOiGHD改善了低脂和高脂喂养小鼠的全身胰岛素敏感性。与改善的胰岛素敏感性一致，间接量热法显示AOiGHD小鼠与GH完整对照相比优先利用碳水化合物进行能量代谢。在高脂肪而非低脂肪喂养的AOiGHD小鼠中，脂肪量增加，肝脏脂质降低，葡萄糖清除率和胰岛素输出受损。这些结果表明，与年龄相关的GH下降有助于保持全身胰岛素敏感性，并在适度热量摄入的情况下，防止代谢功能的恶化。然而，在过量热量摄入的情况下，低GH导致胰岛素输出受损，从而可能导致糖尿病的发展。
Growth hormone (GH) inhibits fat accumulation and promotes protein accretion, therefore the fall in GH observed with weight gain and normal aging may contribute to metabolic dysfunction. To directly test this hypothesis a novel mouse model of adult onset-isolated GH deficiency (AOiGHD) was generated by cross breeding rat GH promoter-driven Cre recombinase mice (Cre) with inducible diphtheria toxin receptor mice (iDTR) and treating adult Cre+/−,iDTR+/− offspring with DT to selectively destroy the somatotrope population of the anterior pituitary gland, leading to a reduction in circulating GH and IGF-I levels. DT-treated Cre−/−,iDTR+/− mice were used as GH-intact controls. AOiGHD improved whole body insulin sensitivity in both low-fat and high-fat fed mice. Consistent with improved insulin sensitivity, indirect calorimetry revealed AOiGHD mice preferentially utilized carbohydrates for energy metabolism, as compared to GH-intact controls. In high-fat, but not low-fat fed AOiGHD mice, fat mass increased, hepatic lipids decreased and glucose clearance and insulin output were impaired. These results suggest the age-related decline in GH helps to preserve systemic insulin sensitivity, and in the context of moderate caloric intake, prevents the deterioration in metabolic function. However, in the context of excess caloric intake, low GH leads to impaired insulin output, and thereby could contribute to the development of diabetes.
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影响因子：
4
作者：
Jensen, J;Galsgaard, ED;Nielsen, JH
通讯作者：
Nielsen, JH
影响因子：
4.8
作者：
Luque, Raul M.;Kineman, Rhonda D.
通讯作者：
Kineman, Rhonda D.
影响因子：
48
作者：
Buch, T;Heppner, FL;Waisman, A
通讯作者：
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影响因子：
4.1
作者：
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通讯作者：
Waschek, James A.
DOI：
10.1152/ajpendo.00423.2003
发表时间：
2004-09-01
影响因子：
5.1
作者：
Liu, JL;Coschigano, KT;Liu, YL
通讯作者：
Liu, YL