Department of Anatomy, Cell Biology and Physiology and Biophysics, Institute of Biology, Universidade Estadual de Campinas - UNICAMP, Campinas, SP, Brazil.
Biol Res. 2011;44(3):251-7. Epub 2011 Nov 7.
Chronic administration of glucocorticoids induces insulin resistance that is compensated by an increase in p-cell function and mass. Since insulin signaling is involved in the control of p-cell function and mass, we investigated the content of insulin pathway proteins in pancreatic islets. Rats were made insulin resistant by daily administration of dexamethasone (1mg/kg, b.w., i.p.) for 5 consecutive days (DEX), whilst control rats received saline (CTL). Circulating insulin and insulin released from isolated islets were measured by radioimmunoassay whereas the content of proteins was analyzed by Western blotting. DEX rats were hyperinsulinemic and exhibited augmented insulin secretion in response to glucose (P < 0.01). The IRa-subunit, IRS-1, Shc, AKT, p-p70S6K, ERK1/2, p-ERK1/2, and glucocorticoid receptor protein levels were similar between DEX and CTL islets. However, the IRp-subunit, p-IRp-subunit, IRS-2, PI3-K, p-AKT and p70S6K protein contents were increased in DEX islets (P < 0.05). We conclude that IRS-2 may have a major role, among the immediate substrates of the insulin receptor, to link activated receptors to downstream signaling components related to islet function and growth in this insulin-resistant rat model.
长期给予糖皮质激素会导致胰岛素抵抗，这种抵抗会通过β细胞功能和数量的增加得到代偿。由于胰岛素信号转导参与了β细胞功能和数量的控制，我们研究了胰岛中胰岛素通路蛋白的含量。通过连续 5 天每天给予地塞米松（1mg/kg，体重，腹腔内）使大鼠产生胰岛素抵抗（DEX），而对照组大鼠给予生理盐水（CTL）。通过放射免疫测定法测量循环胰岛素和从分离的胰岛中释放的胰岛素，而蛋白质含量则通过 Western 印迹进行分析。DEX 大鼠表现为高胰岛素血症，并对葡萄糖表现出增强的胰岛素分泌（P < 0.01）。DEX 和 CTL 胰岛之间的 IRa 亚基、IRS-1、Shc、AKT、p-p70S6K、ERK1/2、p-ERK1/2 和糖皮质激素受体蛋白水平相似。然而，DEX 胰岛中的 IRp 亚基、p-IRp 亚基、IRS-2、PI3-K、p-AKT 和 p70S6K 蛋白含量增加（P < 0.05）。我们的结论是，在胰岛素受体的即刻底物中，IRS-2 可能在这个胰岛素抵抗大鼠模型中发挥主要作用，将激活的受体与与胰岛功能和生长相关的下游信号成分联系起来。
