Gettys T W, Watson P M, Taylor I L, Collins S
Department of Medicine, Medical University of South Carolina, Charleston 29425, USA.
Int J Obes Relat Metab Disord. 1997 Oct;21(10):865-73. doi: 10.1038/sj.ijo.0800479.
To investigate the role of hypercorticism in the development of compromised beta-adrenergic signalling in adipocytes of mature C57BL/6J-ob/ob mice. DESIGN AND EXPERIMENTAL UNITS: Mature male ob/ob mice and their lean littermates were treated with vehicle or the specific glucocorticoid receptor (GR) antagonist, RU-486 (30 mg/kg bw/d) for 21 d.
Blood glucose, serum insulin, adipocyte Glut-4 expression, adipocyte Gs alpha expression, adenylylcyclase activation by beta-adrenergic receptor (beta-AR) agonists in adipocyte membranes and mRNA levels for beta 1-, beta 2- and beta 3-adrenergic receptor subtypes in adipocytes.
RU-486 reduced blood glucose levels in ob/ob mice to levels that were not different from lean mice. RU-486 also reduced serum insulin by approximately 50% in ob/ob mice, but failed to restore depressed Gs alpha or GLUT-4 expression in adipocytes of ob/ob mice. RU-486 produced a two-fold increase in beta 3-AR mRNA in ob/ob mice and a small but significant improvement in isoprenaline-mediated adenylylcyclase activation.
The present results indicate that glucocorticoid antagonism ameliorates diabetic symptoms of the mature ob/ob mouse, but does not lessen their obesity or fully reverse deficient expression and function of components of the adipocyte beta-adrenergic signalling cascade.
研究高皮质醇血症在成熟C57BL/6J-ob/ob小鼠脂肪细胞中β-肾上腺素能信号受损发展过程中的作用。
成熟雄性ob/ob小鼠及其瘦的同窝小鼠分别接受载体或特异性糖皮质激素受体（GR）拮抗剂RU-486（30 mg/kg体重/天）处理21天。
血糖、血清胰岛素、脂肪细胞葡萄糖转运蛋白4（Glut-4）表达、脂肪细胞Gsα表达、脂肪细胞膜中β-肾上腺素能受体（β-AR）激动剂介导的腺苷酸环化酶激活以及脂肪细胞中β1-、β2-和β3-肾上腺素能受体亚型的mRNA水平。
RU-486将ob/ob小鼠的血糖水平降至与瘦小鼠无异的水平。RU-486还使ob/ob小鼠的血清胰岛素降低了约50%，但未能恢复ob/ob小鼠脂肪细胞中Gsα或葡萄糖转运蛋白4（GLUT-4）的表达。RU-486使ob/ob小鼠的β3-AR mRNA增加了两倍，并使异丙肾上腺素介导的腺苷酸环化酶激活有小幅但显著的改善。
目前的结果表明，糖皮质激素拮抗作用改善了成熟ob/ob小鼠的糖尿病症状，但并未减轻其肥胖程度，也未完全逆转脂肪细胞β-肾上腺素能信号级联反应成分的表达和功能缺陷。
