In vitro effects of a sulfonylurea on insulin action in adipocytes. Potentiation of insulin-stimulated hexose transport.
In vitro effects of a sulfonylurea on insulin action in adipocytes. Potentiation of insulin-stimulated hexose transport.
复制标题
磺酰脲类药物对脂肪细胞胰岛素作用的体外影响。
DOI：
10.1172/jci110257
复制
发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Lockwood,DH
中科院分区：
文献类型：
--
作者：
Maloff,BL;Lockwood,DH
以大鼠附睾腺脂肪组织为模型，研究了口服磺脲类药物妥拉扎胺(S)在有或无作用下发挥胰外降血糖作用的机制。比较从培养组织中分离的脂肪细胞的胰岛素结合、己糖转运和葡萄糖代谢。与早先报道的磺脲类药物改变胰岛素结合不同，托拉沙胺治疗不会改变受体数量和亲和力。在没有胰岛素的情况下，葡萄糖类似物2-脱氧葡萄糖和3-0-甲基葡萄糖的摄取也没有变化。然而，在每种激素浓度(0.4-40 ng/ml)下，暴露于托拉扎胺可使胰岛素的刺激效应增强约30%。这种增强作用依赖于托拉西胺的浓度(0.003-0.3 mg/ml)，在治疗水平上效果最好。体内的托拉扎胺类似物的降血糖活性在体外既不能增强基础摄取，也不能增强胰岛素刺激的摄取。在胰岛素存在的情况下，0.1-5.0 mM葡萄糖转化为二氧化碳和总脂的作用也被托拉扎胺增强。该药物不能直接刺激基础葡萄糖摄取的同时，它对葡萄糖代谢也缺乏影响。在50 mM葡萄糖中，转运不再是限速的，在没有或存在胰岛素的情况下，托拉扎胺不能增强新陈代谢。这些研究表明，托拉扎胺在体外改变了受体后的胰岛素作用，而不影响受体，并提示胰岛素刺激的己糖转运是磺脲类药物在脂肪组织中起降血糖作用的细胞过程。
The mechanism(s) by which the oral sulfonylurea, tolazamide, exerts its extrapancreatic hypoglycemic effects was studied using rat epididymal adipose tissue maintained 20-44 h in the presence or absence of the drug. Insulin binding, hexose transport and glucose metabolism were compared in adipocytes isolated from the cultured tissue. In contrast to earlier reports that suggested that sulfonylureas alter the binding of insulin, neither receptor number nor affinity were changed by tolazamide treatment. The uptake of the glucose analogs 2-deoxyglucose and 3-0-methylglucose in the absence of insulin (i.e., basal) was also unchanged. However, exposure to tolazamide resulted in a potentiation of the stimulatory effects of insulin by approximately 30% at each hormone concentration assayed (0.4-40 ng/ml). This potentiation was dependent on the tolazamide concentration (0.003-0.30 mg/ml), with a maximal effect observed at therapeutic levels. A tolazamide analog hypoglycemic activity in vivo was found not to enhance either basal or insulin-stimulated uptake in vitro. Conversion of 0.1-5.0 mM glucose to CO2 and total lipids in the presence of insulin was also potentiated by tolazamide treatment. The inability of the drug to directly stimulate basal glucose uptake was paralleled by its lack of effect on glucose metabolism. At 50 mM glucose, where transport is no longer rate-limiting, tolazamide did not potentiate metabolism in the absence or the presence of insulin. These studies demonstrate that tolazamide in vitro alters postreceptor insulin action without influencing the receptor, and suggests insulin-stimulated hexose transport as the cellular process responsible for the hypoglycemic effect of sulfonyureas in adipose tissue.