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人类骨骼肌细胞分化与肌源性标志物的变化以及胰岛素介导的丝裂原活化蛋白激酶(MAPK)和蛋白激酶B(PKB)磷酸化增强有关。

Human skeletal muscle cell differentiation is associated with changes in myogenic markers and enhanced insulin-mediated MAPK and PKB phosphorylation.

作者信息

Al-Khalili L, Krämer D, Wretenberg P, Krook A

机构信息

Department of Surgical Science, Karolinska Institutet, Stockholm, Sweden.

出版信息

Acta Physiol Scand. 2004 Apr;180(4):395-403. doi: 10.1111/j.1365-201X.2004.01259.x.

DOI:10.1111/j.1365-201X.2004.01259.x
PMID:15030381
Abstract

AIM

We hypothesized that myogenic differentiation of HSMC would yield a more insulin responsive phenotype.

METHODS

We assessed expression of several proteins involved in insulin action or myogenesis during differentiation of primary human skeletal muscle cultures (HSMC).

RESULTS

Differentiation increased creatine kinase activity and expression of desmin and myocyte enhancer factor (MEF)2C. No change in expression was observed for big mitogen-activated protein kinase (BMK1/ERK5), MEF2A, insulin receptor (IR), hexokinase II, and IR substrates 1 and 2, while expression of glycogen synthase, extracellular signal-regulated kinase 1 and 2 (ERK1/2 MAP kinase) and the insulin responsive aminopeptidase increased after differentiation. In contrast to protein kinase B (PKB)a, expression of (PKB)b increased, with differentiation. Both basal and insulin-stimulated PI 3-kinase activity increased with differentiation. Insulin-mediated phosphorylation of PKB and ERK1/2 MAP kinase increased after differentiation.

CONCLUSION

Components of the insulin-signalling machinery are expressed in myoblast and myotube HSMC; however, insulin responsiveness to PKB and ERK MAP kinase phosphorylation increases with differentiation.

摘要

目的

我们假设人骨骼肌细胞(HSMC)的肌源性分化会产生更具胰岛素反应性的表型。

方法

我们评估了原代人骨骼肌培养物(HSMC)分化过程中几种参与胰岛素作用或肌生成的蛋白质的表达。

结果

分化增加了肌酸激酶活性以及结蛋白和肌细胞增强因子(MEF)2C的表达。大丝裂原活化蛋白激酶(BMK1/ERK5)、MEF2A、胰岛素受体(IR)、己糖激酶II以及IR底物1和2的表达未观察到变化,而糖原合酶、细胞外信号调节激酶1和2(ERK1/2丝裂原活化蛋白激酶)以及胰岛素反应性氨肽酶的表达在分化后增加。与蛋白激酶B(PKB)α相反,PKBβ的表达随分化而增加。基础和胰岛素刺激的PI 3激酶活性均随分化而增加。分化后胰岛素介导的PKB和ERK1/2丝裂原活化蛋白激酶的磷酸化增加。

结论

胰岛素信号传导机制的组成部分在成肌细胞和肌管HSMC中表达;然而,胰岛素对PKB和ERK丝裂原活化蛋白激酶磷酸化的反应性随分化而增加。

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