Phorbol ester provokes insulin-like effects on glucose transport, amino acid uptake, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes.
Phorbol ester provokes insulin-like effects on glucose transport, amino acid uptake, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes.
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DOI：
10.1210/endo-116-6-2650
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发表时间：
1985-06
期刊：
影响因子：
4.8
通讯作者：
R. Farese;M. Standaert;D. Barnes;J. Davis;R. Pollet
中科院分区：
文献类型：
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作者：
R. Farese;M. Standaert;D. Barnes;J. Davis;R. Pollet
我们评估了二酰甘油在胰岛素作用中作为第二信使发挥作用的可能性。为此，我们使用了12-O-十四酰佛波醇13-乙酸酯(TPA)来模拟BC3H-1心肌细胞中的二酰甘油。与胰岛素一样，TPA可刺激成熟的胰岛素反应性BC3H-1培养的心肌细胞2-脱氧葡萄糖转运和丙酮酸脱氢酶活性的快速增加。TPA还刺激氨基酸的摄取，如对α-甲氨基异丁酸的摄取；这一效应的相对缓慢的时间进程与胰岛素的时间进程平行。相比之下，TPA对未分化的BC3H-1成肌细胞的作用不明显，这些细胞对胰岛素也没有反应。心肌细胞中的胰岛素样效应似乎是TPA所特有的，TPA是一种具有生物活性的佛波二酯，它可以激活蛋白激酶C，因为其他被测试的佛波醇衍生物没有作用。最大有效浓度的TPA和胰岛素的作用是非相加的。两种人工合成的甘油二酯，1，2-二甘油烯和1-油酰基-2-乙酰甘油，也对2-脱氧葡萄糖的转运产生胰岛素样作用。由于胰岛素在这些细胞中迅速增加二酰甘油的水平，而TPA在生物化学上模仿二酰甘油，因此胰岛素可能通过二酰甘油的变化来控制细胞过程。
We evaluated the possibility that diacylglycerol may function as a second messenger in insulin action. To this end, we employed 12-O-tetradecanoyl phorbol 13-acetate (TPA) to mimic diacylglycerol in BC3H-1 myocytes. Like insulin, TPA provoked rapid increases in 2-deoxyglucose transport and pyruvate dehydrogenase activity in mature insulin-responsive BC3H-1 cultured myocytes. TPA also stimulated amino acid uptake, as evidenced by uptake of alpha-methylaminoisobutyric acid; the relatively slow time course of this effect paralleled that of insulin. In contrast, the effects of TPA were not apparent in undifferentiated BC3H-1 myoblasts, which were also unresponsive to insulin. The insulin-like effects in the myocytes appeared to be specific for TPA, the biologically active phorbol diester which activates protein kinase C, as other tested phorbol derivatives were without effect. Effects of maximally effective concentrations of TPA and insulin were nonadditive. Two synthetic diacylglycerols, 1,2-diolien and 1-oleoyl-2-acetyl-sn-glycerol, also provoked insulin-like effects on 2-deoxyglucose transport. Since insulin rapidly increases diacylglycerol levels in these cells, and TPA mimics diacylglycerol biochemically, it is possible that insulin may control cellular processes through changes in diacylglycerol.