McCaleb M L, Maloff B L, Nowak S M, Lockwood D H
Diabetes Care. 1984 May-Jun;7 Suppl 1:42-6.
We have examined the nonpancreatic actions of sulfonylureas on multiple aspects of insulin responsiveness in two target tissues for insulin, liver and fat. In vivo administration of tolazamide and glipizide reduced significantly the postabsorptive serum glucose levels in rats without altering the levels of insulin. This was consistent with extrapancreatic sites of drug action. The number and affinity of hepatic insulin receptors was not different from those of control rats. Using a tissue culture system for rat adipose tissue, a 20-h treatment with sulfonylureas markedly potentiated insulin action in fat cells. The primary augmentation was at the level of insulin-stimulated glucose transport. Again, there was no alteration of the insulin receptors located on the adipose tissue. Furthermore, consistent with the lack of an influence on insulin-induced receptor loss after in vitro treatment with sulfonylureas, the in vivo administration of these agents did not alter the transglutaminase activity in rat hepatic tissue. The data demonstrate that sulfonylureas potentiate the responsiveness of the target tissues for insulin. Thus, these hypoglycemic agents probably act by correcting some of the cellular lesions associated with the insulin resistance in type II diabetes mellitus.
我们研究了磺脲类药物对胰岛素的两个靶组织（肝脏和脂肪）胰岛素反应性多个方面的非胰腺作用。在大鼠体内给予甲苯磺丁脲和格列吡嗪可显著降低吸收后血清葡萄糖水平，而不改变胰岛素水平。这与药物作用的胰腺外部位一致。肝脏胰岛素受体的数量和亲和力与对照大鼠无异。使用大鼠脂肪组织的组织培养系统，用磺脲类药物处理20小时可显著增强脂肪细胞中的胰岛素作用。主要增强作用发生在胰岛素刺激的葡萄糖转运水平。同样，脂肪组织上的胰岛素受体没有改变。此外，与磺脲类药物体外处理后对胰岛素诱导的受体丢失无影响一致，这些药物的体内给药并未改变大鼠肝脏组织中的转谷氨酰胺酶活性。数据表明磺脲类药物可增强胰岛素靶组织的反应性。因此，这些降糖药物可能通过纠正与II型糖尿病胰岛素抵抗相关的一些细胞病变来发挥作用。
