Joost H G, Arend W, Holze S A
Biochem Pharmacol. 1982 Apr 1;31(7):1227-31. doi: 10.1016/0006-2952(82)90008-9.
In isolated fat cells of the rat the in vitro and in vivo effects of tolbutamide on insulin binding and insulin response were studied. 450 mg tolbutamide/kg/day given for 7 days significantly increased the binding of insulin to isolated adipocytes. The binding curves reflected an increase in the number of receptor sites rater than in the affinity. The effect was associated with an enhanced response to insulin of the adipose tissue, since the fat cells obtained from animals treated with tolbutamide converted significantly more glucose to lipids in the presence of insulin than those obtained from the control group. However, the augmentation of insulin binding sites was observed only at a large tolbutamide dosage, which reduced the pancreatic insulin content, the secretory response of the isolated pancreas, and the serum insulin levels. Smaller doses, sufficient to produce metabolic effects via a stimulation of insulin secretion, did not provide additional insulin binding sites. When added in vitro to the binding assay or to adipose tissue incubated for 16 h, tolbutamide failed to increase insulin binding of the fat cells. It is suggested, therefore, that the effects produced by tolbutamide after in vivo treatment reflect an indirect rather than a direct action of the sulphonylurea.
在大鼠的分离脂肪细胞中，研究了甲苯磺丁脲对胰岛素结合及胰岛素反应的体内和体外效应。以450毫克甲苯磺丁脲/千克/天的剂量给药7天，可显著增加胰岛素与分离脂肪细胞的结合。结合曲线反映出受体位点数量的增加而非亲和力的增加。该效应与脂肪组织对胰岛素反应的增强相关，因为在胰岛素存在的情况下，从用甲苯磺丁脲处理的动物获得的脂肪细胞比从对照组获得的脂肪细胞能将更多的葡萄糖转化为脂质。然而，仅在大剂量甲苯磺丁脲时才观察到胰岛素结合位点的增加，此时胰腺胰岛素含量、分离胰腺的分泌反应及血清胰岛素水平均降低。足以通过刺激胰岛素分泌产生代谢效应的较小剂量，并未提供额外的胰岛素结合位点。当在体外添加到结合试验或培养16小时的脂肪组织中时，甲苯磺丁脲未能增加脂肪细胞的胰岛素结合。因此，有人提出，甲苯磺丁脲在体内治疗后产生的效应反映了磺脲类药物的间接而非直接作用。
