Martínez C, Ruiz P, Andrés A, Satrústegui J, Carrascosa J M
Departamento Biología Molecular, C.S.I.C., Universidad Autónoma de Madrid, Spain.
Biochem J. 1989 Oct 1;263(1):267-72. doi: 10.1042/bj2630267.
Late gestation is associated with insulin resistance in rats and humans. It has been reported that rats at term gestation show active hepatic gluconeogenesis and glycogenolysis, and diminished lipogenesis, despite normal or mildly elevated plasma insulin concentrations, indicating a state of resistance to the hormone action. Since autophosphorylation of the insulin receptor has been reported to play a key role in the hormone signal transduction, we have partially purified plasma-membrane liver insulin receptors from virgin and 22-day-pregnant rats and studied their binding and kinase activities. (1) Insulin binding to partially purified receptors does not appear to be influenced by gestation, as indicated by the observed KD and Bmax. values. (2) The rate of autophosphorylation and the maximal 32P incorporation into the receptor beta-subunit from pregnant rats at saturating concentrations of insulin are markedly decreased with respect to the corresponding values for virgin rats. (3) The diminished autophosphorylation rate was due to a decreased responsiveness of the kinase activity to the action of insulin. (4) Phosphorylation of the exogenous substrates casein and poly(Glu80Tyr20) by insulin-receptor kinase was also less when receptors from pregnant rats were used. These results show the existence of an impairment at the receptor kinase level of the insulin signalling mechanism that might be related to the insulin-resistant state characteristic of term gestation in rats.
妊娠晚期与大鼠和人类的胰岛素抵抗有关。据报道，足月妊娠的大鼠尽管血浆胰岛素浓度正常或轻度升高，但仍表现出活跃的肝糖异生和糖原分解，且脂肪生成减少，这表明存在对激素作用的抵抗状态。由于胰岛素受体的自磷酸化在激素信号转导中起关键作用，我们从未孕大鼠和妊娠22天的大鼠中部分纯化了肝细胞膜胰岛素受体，并研究了它们的结合和激酶活性。（1）如观察到的KD和Bmax值所示，胰岛素与部分纯化受体的结合似乎不受妊娠影响。（2）在胰岛素饱和浓度下，妊娠大鼠受体β亚基的自磷酸化速率和最大32P掺入量相对于未孕大鼠的相应值明显降低。（3）自磷酸化速率降低是由于激酶活性对胰岛素作用的反应性降低。（4）当使用妊娠大鼠的受体时，胰岛素受体激酶对外源底物酪蛋白和聚（Glu80Tyr20）的磷酸化作用也较小。这些结果表明，胰岛素信号传导机制的受体激酶水平存在损伤，这可能与大鼠足月妊娠时的胰岛素抵抗状态有关。
