Jacobs D B, Jung C Y
J Biol Chem. 1985 Mar 10;260(5):2593-6.
Sulfonylureas potentiate the insulin-induced stimulation of glucose transport in adipocytes. In order to elucidate the molecular mechanism of this potentiation, effects of a long-term (48-h) incubation with glyburide (2 micrograms/ml) on the relative sizes of the plasma membrane, the microsome, and the total membrane pools of the glucose-sensitive cytochalasin B binding were studied for basal and insulin-stimulated adipocytes. The drug treatment potentiated an insulin-induced stimulation of 3-O-methyl-D-glucose flux by 31 to 45%, with little effect on the basal flux. The same drug treatment increased the plasma membrane pool size of the glucose-sensitive cytochalasin B binding in the insulin-stimulated adipocytes with a concomitant decrease in the microsomal pool size. This effect was minimal, if any, in basal adipocytes. The drug treatment did not affect the total glucose-sensitive, cytochalasin B binding capacity of adipocyte membranes. These results indicate that the drug treatment increases the insulin-induced recruitment of the glucose carrier from the microsome to the plasma membrane by 27-31%. It is concluded that potentiation of the insulin-induced stimulation of the hexose transport by sulfonylureas is mainly due to a potentiation of the insulin-induced recruitment of the glucose carrier.
磺脲类药物可增强胰岛素对脂肪细胞葡萄糖转运的刺激作用。为阐明这种增强作用的分子机制,研究了用格列本脲(2微克/毫升)进行长期(48小时)孵育对基础状态及胰岛素刺激的脂肪细胞中质膜、微粒体以及葡萄糖敏感的细胞松弛素B结合的总膜池相对大小的影响。药物处理使胰岛素诱导的3 - O - 甲基 - D - 葡萄糖通量刺激增强了31%至45%,而对基础通量影响很小。同样的药物处理增加了胰岛素刺激的脂肪细胞中葡萄糖敏感的细胞松弛素B结合的质膜池大小,同时微粒体池大小相应减小。在基础状态的脂肪细胞中,这种作用即使有也是最小的。药物处理不影响脂肪细胞膜的总葡萄糖敏感的细胞松弛素B结合能力。这些结果表明,药物处理使胰岛素诱导的葡萄糖载体从微粒体向质膜的募集增加了27% - 31%。得出的结论是,磺脲类药物对胰岛素诱导的己糖转运的增强作用主要是由于对胰岛素诱导的葡萄糖载体募集的增强。