Corbould Anne, Dunaif Andrea
Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Metabolism. 2007 May;56(5):716-22. doi: 10.1016/j.metabol.2006.12.021.
Selective resistance to the effects of insulin on glucose metabolism in skeletal muscle and adipose tissue is a key feature of polycystic ovary syndrome (PCOS). The pathogenesis of insulin resistance in skeletal muscle in PCOS involves interaction of in vivo environmental factors with intrinsic defects in insulin signaling. We aimed to determine whether (1) intrinsic defects in insulin action/signaling and cytokine secretion were present in adipose cells in PCOS and (2) insulin resistance can be induced in control adipose cells by culture in medium conditioned by insulin-resistant PCOS fibroblasts. Subcutaneous abdominal preadipocytes from obese women with PCOS (n = 7) and age- and body mass index-matched controls (n = 5) were cultured for several generations in vitro. Basal and insulin-stimulated glycogen synthesis and basal glucose transport did not differ in the preadipocytes from women with PCOS and controls. Abundance of insulin receptor (IR) beta subunit, insulin receptor substrate (IRS) 1 and 2, p85 subunit of phosphatidylinositol 3-kinase, and extracellular signal-regulated kinase (ERK)1/2 activation did not differ. Secretion of tumor necrosis factor alpha and interleukin 6 did not differ. Insulin action on glycogen synthesis in control preadipocytes was not altered by coculture with or growth in media conditioned by PCOS skin fibroblasts with constitutive serine phosphorylation of IRbeta subunit (IR ser+), indicating that IR ser+ cells do not secrete an insulin resistance-inducing factor. We conclude that in contrast to skeletal muscle and skin fibroblasts, there is no evidence for intrinsic defects in insulin signaling in the PCOS adipose cell lineage, indicating that insulin resistance in these cells is likely due to factors in the in vivo environment.
对胰岛素在骨骼肌和脂肪组织中葡萄糖代谢作用的选择性抵抗是多囊卵巢综合征（PCOS）的一个关键特征。PCOS患者骨骼肌中胰岛素抵抗的发病机制涉及体内环境因素与胰岛素信号转导内在缺陷的相互作用。我们旨在确定：（1）PCOS患者脂肪细胞中是否存在胰岛素作用/信号转导和细胞因子分泌的内在缺陷；（2）通过在胰岛素抵抗的PCOS成纤维细胞条件培养基中培养，能否在对照脂肪细胞中诱导出胰岛素抵抗。将来自肥胖PCOS女性（n = 7）以及年龄和体重指数匹配的对照女性（n = 5）的腹部皮下前脂肪细胞进行了几代体外培养。PCOS女性和对照女性的前脂肪细胞中，基础和胰岛素刺激的糖原合成以及基础葡萄糖转运没有差异。胰岛素受体（IR）β亚基、胰岛素受体底物（IRS）1和2、磷脂酰肌醇3激酶的p85亚基以及细胞外信号调节激酶（ERK）1/2的活化丰度没有差异。肿瘤坏死因子α和白细胞介素6的分泌没有差异。与IRβ亚基组成性丝氨酸磷酸化的PCOS皮肤成纤维细胞共培养或在其条件培养基中生长，均未改变对照前脂肪细胞中胰岛素对糖原合成的作用，这表明IR ser+细胞不会分泌诱导胰岛素抵抗的因子。我们得出结论，与骨骼肌和皮肤成纤维细胞不同，没有证据表明PCOS脂肪细胞系中存在胰岛素信号转导的内在缺陷，这表明这些细胞中的胰岛素抵抗可能是由于体内环境中的因素所致。
