Cordoba-Chacon Jose, Gahete Manuel D, McGuinness Owen P, Kineman Rhonda D
Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois; Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;
Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois; Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba/Hospital Universitario Reina Sofia, and CIBER de la Fisiopatología de la Obesidad y Nutrición, Córdoba, Spain; and.
Am J Physiol Endocrinol Metab. 2014 Nov 15;307(10):E928-34. doi: 10.1152/ajpendo.00420.2014. Epub 2014 Sep 30.
A reciprocal relationship between insulin sensitivity and glucose tolerance has been reported in some mouse models and humans with isolated changes in growth hormone (GH) production and signaling. To determine if this could be explained in part by tissue-specific changes in insulin sensitivity, hyperinsulinemic-euglycemic clamps were performed in mice with adult-onset, isolated GH deficiency and in mice with elevated endogenous GH levels due to somatotrope-specific loss of IGF-I and insulin receptors. Our results demonstrate that circulating GH levels are negatively correlated with insulin-mediated glucose uptake in muscle but positively correlated with insulin-mediated suppression of hepatic glucose production. A positive relationship was also observed between GH levels and endpoints of hepatic lipid metabolism known to be regulated by insulin. These results suggest hepatic insulin resistance could represent an early metabolic defect in GH deficiency.
在一些生长激素（GH）产生和信号传导发生孤立变化的小鼠模型和人类中，已报道胰岛素敏感性和葡萄糖耐量之间存在相互关系。为了确定这是否部分可以通过胰岛素敏感性的组织特异性变化来解释，对成年期发病、孤立性GH缺乏的小鼠以及由于生长激素细胞特异性缺失IGF-I和胰岛素受体而导致内源性GH水平升高的小鼠进行了高胰岛素-正常血糖钳夹试验。我们的结果表明，循环GH水平与肌肉中胰岛素介导的葡萄糖摄取呈负相关，但与胰岛素介导的肝葡萄糖生成抑制呈正相关。在GH水平与已知受胰岛素调节的肝脂质代谢终点之间也观察到正相关关系。这些结果表明，肝脏胰岛素抵抗可能是GH缺乏症早期的代谢缺陷。
