磺脲类药物刺激肝脏果糖-2,6-二磷酸的生成，其程度与降血糖作用成正比。

Sulfonylurea stimulates liver fructose-2,6-bisphosphate formation in proportion to its hypoglycemic action.

作者信息

Hatao K, Kaku K, Matsuda M, Tsuchiya M, Kaneko T

出版信息

Diabetes Res Clin Pract. 1985 Mar;1(1):49-53. doi: 10.1016/s0168-8227(85)80028-0.

Abstract

The effects of 5 sulfonylureas on fructose-2,6-bisphosphate (F-2,6-P2) formation using isolated perfused rat liver were examined. All sulfonylureas examined stimulated dose-dependent formation of the activator in a limited range of the concentration. A maximum effect on F-2,6-P2 formation was observed at the concentration of 10(-3) M of tolbutamide or chlorpropamide, at 10(-4) M of gliclazide or acetohexamide and at 10(-6) M of glibenclamide. These concentrations of sulfonylurea correspond with those in blood when therapeutical doses of the drug are administered orally. Sulfonamide and biguanide did not show any stimulatory effect on F-2,6-P2 level. The results demonstrate that stimulation of liver F-2,6-P2 formation is a common characteristic of sulfonylureas and suggest strongly that one of the extrapancreatic actions of sulfonylurea is stimulation of F-2,6-P2 formation followed by enhancement of glycolysis and inhibition of gluconeogenesis in the liver.

摘要

研究了5种磺脲类药物对使用离体灌注大鼠肝脏生成果糖-2,6-二磷酸（F-2,6-P2）的影响。所有检测的磺脲类药物在有限的浓度范围内均能刺激该激活剂的剂量依赖性生成。在甲苯磺丁脲或氯磺丙脲浓度为10⁻³M、格列齐特或醋磺己脲浓度为10⁻⁴M以及格列本脲浓度为10⁻⁶M时，观察到对F-2,6-P2生成的最大效应。这些磺脲类药物的浓度与口服治疗剂量药物时血液中的浓度相对应。磺胺类药物和双胍类药物对F-2,6-P2水平未显示出任何刺激作用。结果表明，刺激肝脏F-2,6-P2生成是磺脲类药物的共同特征，并强烈提示磺脲类药物的胰腺外作用之一是刺激F-2,6-P2生成，随后增强肝脏中的糖酵解并抑制糖异生。