EFFECTS OF CONTRACTILE ACTIVITY ON TYROSINE PHOSPHOPROTEINS AND PI 3-KINASE ACTIVITY IN RAT SKELETAL-MUSCLE
EFFECTS OF CONTRACTILE ACTIVITY ON TYROSINE PHOSPHOPROTEINS AND PI 3-KINASE ACTIVITY IN RAT SKELETAL-MUSCLE
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DOI：
10.1152/ajpendo.1995.268.5.e987
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发表时间：
1995-05-01
影响因子：
5.1
通讯作者：
SMITH, RJ
中科院分区：
文献类型：
--
作者：
GOODYEAR, LJ;GIORGINO, F;SMITH, RJ
胰岛素刺激信号传导反应，包括胰岛素受体自磷酸化和酪氨酸激酶活化、胰岛素受体底物-1（IRS-1）酪氨酸磷酸化和磷脂酰肌醇3-激酶（PI 3-激酶）活化。肌肉收缩具有与胰岛素类似的代谢作用，收缩可以增加胰岛素敏感性，但对介导收缩作用的分子信号知之甚少。为了研究肌肉收缩对胰岛素信号传导的影响，在通过电刺激、在没有收缩的情况下最大胰岛素注射或收缩后注射胰岛素来收缩后肢肌肉后研究大鼠。胰岛素增加胰岛素受体和IRS-1的酪氨酸磷酸化，而单独收缩没有影响。注射胰岛素前收缩使胰岛素对受体和IRS-1磷酸化的作用降低20- 25%。未观察到胰岛素和/或收缩引起的其他蛋白质酪氨酸磷酸化增加。单独收缩对PI 3-激酶活性影响不大，但收缩明显减弱胰岛素刺激的IRS-1和胰岛素受体免疫沉淀PI 3-激酶的激活。总之，骨骼肌收缩活动不会导致参与胰岛素信号传导初始步骤的分子的酪氨酸磷酸化。虽然收缩活动增加胰岛素敏感性和骨骼肌的反应性，收缩导致胰岛素刺激的酪氨酸磷酸化和PI 3-激酶活性的矛盾下降。
Insulin stimulates signaling reactions that include insulin receptor autophosphorylation and tyrosine kinase activation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and phosphatidylinositol 3-kinase (PI 3-kinase) activation. Muscle contraction has metabolic effects similar to insulin, and contraction can increase insulin sensitivity, but little is known about the molecular signals that mediate the effects of contraction. To investigate the effects of muscle contraction on insulin signaling, rats were studied after contraction of hindlimb muscles by electrical stimulation, maximal insulin injection in the absence of contraction, or contraction followed by insulin injection. Insulin increased tyrosine phosphorylation of the insulin receptor and IRS-1, whereas contraction alone had no effect. Contraction before insulin injection decreased the insulin effect on receptor and IRS-1 phosphorylation by 20-25%. Increased tyrosine phosphorylation of other proteins by insulin and/or contraction was not observed. Contraction alone had little effect on PI 3-kinase activity, but contraction markedly blunted the insulin-stimulated activation of IRS-1 and insulin receptor-immunoprecipitable PI 3-kinase. In conclusion, skeletal muscle contractile activity does not result in tyrosine phosphorylation of molecules involved in the initial steps of insulin signaling. Although contractile activity increases insulin sensitivity and responsiveness in skeletal muscle, contraction causes a paradoxical decrease in insulin-stimulated tyrosine phosphorylation and PI 3-kinase activity.