Murakami N, Inoue G, Okamoto M, Yoshimasa Y, Kohno S, Hayashi T, Kato K, Kuzuya H, Nakao K
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Kita-ku, Tokyo, Japan.
Life Sci. 1997;60(20):1821-31. doi: 10.1016/s0024-3205(97)00142-2.
We investigated the effect of M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) on glucose transport and the insulin signaling system in mouse-derived 3T3-L1 adipocytes. When M16209 (30 and 100 microM) was added to 3T3-L1 adipocytes and preincubated for 24 hours, the uptake of 2-deoxy-D-[3H]-glucose (2-DG) after insulin stimulation was enhanced. This effect was seen when preincubation with M16209 was performed in the presence of 6 and 20 ng/ml insulin, but M16209 did not increase the response to 600 ng/ml insulin. M16209 (100 microM) did not interfere with (125)I-insulin binding or with tyrosine phosphorylation of the insulin receptor beta-subunit and IRS-1. M16209 (100 microM) also had no effect on the level of glucose transporter (GLUT1 and GLUT4) protein, but it promoted the translocation of intracellular GLUT4 to the plasma membrane. In contrast, M16209 had no effect on the translocation of GLUT1. In summary, M16209 enhanced 2-DG uptake by 3T3-L1 adipocytes. Insulin binding to its receptor, autophosphorylation of the insulin receptor beta-subunit, and tyrosine phosphorylation of IRS-1 were unaffected by M16209. However, translocation of GLUT4 from the intracellular pool to the plasma membrane was facilitated.
我们研究了M16209（1-(3-溴苯并[b]呋喃-2-基磺酰基)乙内酰脲）对小鼠源3T3-L1脂肪细胞中葡萄糖转运及胰岛素信号系统的影响。当将M16209（30和100微摩尔）添加至3T3-L1脂肪细胞并预孵育24小时后，胰岛素刺激后的2-脱氧-D-[3H]-葡萄糖（2-DG）摄取增强。在存在6和20纳克/毫升胰岛素的情况下进行与M16209的预孵育时可观察到这种效应，但M16209并未增加对600纳克/毫升胰岛素的反应。M16209（100微摩尔）不干扰（125）I-胰岛素结合或胰岛素受体β亚基及胰岛素受体底物-1（IRS-1）的酪氨酸磷酸化。M16209（100微摩尔）对葡萄糖转运蛋白（GLUT1和GLUT4）的蛋白水平也无影响，但它促进细胞内GLUT4向质膜的转位。相比之下，M16209对GLUT1的转位没有影响。总之，M16209增强了3T3-L1脂肪细胞对2-DG的摄取。M16209不影响胰岛素与其受体的结合、胰岛素受体β亚基的自身磷酸化以及IRS-1的酪氨酸磷酸化。然而，GLUT4从细胞内池向质膜的转位得到了促进。
