Insulin-stimulated glycogen synthesis in cultured hepatoma cells: differential effects of inhibitors of insulin signaling molecules.
Insulin-stimulated glycogen synthesis in cultured hepatoma cells: differential effects of inhibitors of insulin signaling molecules.
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DOI：
10.3109/10799899809047746
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发表时间：
1998-07
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影响因子：
--
通讯作者：
C. Sung;W. Choi;P. Scalia
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文献类型：
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作者：
C. Sung;W. Choi;P. Scalia
在过度表达人胰岛素受体的大鼠 HTC 肝癌细胞中，胰岛素刺激糖原合成 55-70%。为了研究导致这些细胞中胰岛素刺激糖原合成的受体后信号转导事件，我们采用了途径特异性化学抑制剂，例如 LY294002、雷帕霉素和 PD98059 来抑制磷脂酰肌醇-3-激酶 (PI3K)、p70 核糖体 S6 激酶和丝裂原激活蛋白激酶 (MAPK)激酶/MAPK，分别。 LY294002 (50 microM) 完全消除胰岛素刺激的糖原合成，而雷帕霉素 (2-20 nM) 部分抑制它。 LY294002和雷帕霉素均未显着影响基础糖原合成。然而，PD98059 (100 microM) 显着抑制基础糖原合成，而不影响胰岛素刺激的糖原合成。在这些细胞中，100 nM 的胰岛素使糖原合酶激酶 3 α (GSK3 α) 活性降低 30-35%。 LY294002，但雷帕霉素和 PD98059 均不能消除胰岛素诱导的 GSK3 α 失活。这些数据表明，大鼠 HTC 肝癌细胞中胰岛素刺激的糖原合成主要通过 PI3K 依赖性机制介导。在这些细胞中，PI3K 下游 GSK3 α 的失活可能在胰岛素刺激的糖原合成中发挥作用。
In rat HTC hepatoma cells overexpressing human insulin receptors, insulin stimulated glycogen synthesis by 55-70%. To study postreceptor signaling events leading to insulin-stimulated glycogen synthesis in these cells, we have employed pathway-specific chemical inhibitors such as LY294002, rapamycin and PD98059 to inhibit phosphatidylinositol-3-kinase (PI3K), p70 ribosomal S6 kinase and mitogen-activated protein kinase (MAPK) kinase/MAPK, respectively. LY294002 (50 microM) completely abolished insulin-stimulated glycogen synthesis whereas rapamycin (2-20 nM) partially inhibited it. Neither LY294002 nor rapamycin significantly affected the basal glycogen synthesis. However, PD98059 (100 microM) significantly inhibited the basal glycogen synthesis without affecting insulin-stimulated glycogen synthesis. In these cells, insulin at 100 nM decreased glycogen synthase kinase 3 alpha (GSK3 alpha) activity by 30-35%. LY294002, but neither rapamycin nor PD98059, abolished insulin-induced inactivation of GSK3 alpha. These data suggest that insulin-stimulated glycogen synthesis in rat HTC hepatoma cells is mediated mainly by PI3K-dependent mechanism. In these cells, inactivation of GSK3 alpha, downstream of PI3K, may play a role in insulin-stimulated glycogen synthesis.