Barros L F, Marchant R B, Baldwin S A
Department of Biochemistry and Molecular Biology, University of Leeds, U.K.
Biochem J. 1995 Aug 1;309 ( Pt 3)(Pt 3):731-6. doi: 10.1042/bj3090731.
The signaling pathways responsible for the activation of glucose transport by insulin and by metabolic stress in mammalian cells were studied in Clone 9 cells and 3T3-L1 adipocytes. Exposure of both cell types to azide or insulin markedly increased their glucose uptake capacity (Vmax.) without affecting their apparent affinity for glucose (Km). The effects of azide and insulin were not additive. Wortmannin, a selective inhibitor of phosphatidylinositol (PI) 3-kinase, did not affect stimulation of transport by azide but inhibited insulin-induced glucose transport with a Ki of < 10 nM. ML-9, a putative mitogen-activated protein kinase inhibitor, was equipotent in its inhibition of azide- and insulin-stimulated glucose transport. These findings suggest that multiple signalling cascades are involved in the stimulation of glucose transport in mammalian cells and that PI 3-kinase, an essential link in the pathway by which insulin stimulates glucose transport, is not necessary for the activation of glucose uptake by metabolic stress.
在克隆9细胞和3T3-L1脂肪细胞中研究了哺乳动物细胞中胰岛素和代谢应激激活葡萄糖转运的信号通路。将这两种细胞类型暴露于叠氮化物或胰岛素中，可显著提高它们的葡萄糖摄取能力（Vmax），而不影响它们对葡萄糖的表观亲和力（Km）。叠氮化物和胰岛素的作用不是相加的。渥曼青霉素是一种磷脂酰肌醇（PI）3激酶的选择性抑制剂，它不影响叠氮化物对转运的刺激，但抑制胰岛素诱导的葡萄糖转运，其抑制常数（Ki）<10 nM。ML-9是一种假定的丝裂原活化蛋白激酶抑制剂，它对叠氮化物和胰岛素刺激的葡萄糖转运具有同等的抑制作用。这些发现表明，多种信号级联参与了哺乳动物细胞中葡萄糖转运的刺激，并且PI 3激酶是胰岛素刺激葡萄糖转运途径中的一个重要环节，而代谢应激激活葡萄糖摄取并不需要它。
