Boot J H
Department Veterinary Pharmacology, Pharmacy and Toxicology, Utrecht, The Netherlands.
Cell Struct Funct. 1996 Feb;21(1):1-6. doi: 10.1247/csf.21.1.
The interference of various SH-blocking chemicals with the insulin-controlled regulation of the hepatic carbohydrate metabolism was studied in rat hepatocyte primary cultures. The organic mercurials PCMB, PCMBS, mersalyl the disulphide agents DTP, CPDS, disulfiram and the SH-alkylating reagent NEM were used as experimental SH-blocking model compounds. All studied compounds, except for NEM, induced an increased glycogen deposition comparable with the physiological insulin-induced glycogen-deposition. PCMBS appeared to be the most effective insulin-mimicking anabolic trigger. The action of the insulin molecule itself was potentiated by PCMBS as well as demonstrated by increased glycogen deposition, induced pyruvate kinase (PK) and decreased phosphoenol-pyruvate carboxykinase (PEP-CK) activity. However, cell-exposure to insulin and PCMBS in relatively high doses was destructive, as demonstrated by decreased glycogen levels, most probably as a result of insulin-receptor overstimulation and metabolic stress. Thus, SH-blocking compounds are able to trigger insulin-dependent metabolic processes. The relatively non-permeant organic mercurial PCMBS proved to be the most effective insulin-mimicking SH-blocking compound.
在大鼠肝细胞原代培养中研究了各种SH阻断化学物质对胰岛素控制的肝脏碳水化合物代谢调节的干扰。有机汞化合物PCMB、PCMBS、汞撒利、二硫化物试剂DTP、CPDS、双硫仑以及SH烷基化试剂NEM被用作实验性SH阻断模型化合物。除NEM外，所有研究的化合物都诱导了糖原沉积增加，与生理性胰岛素诱导的糖原沉积相当。PCMBS似乎是最有效的胰岛素模拟合成代谢触发剂。PCMBS增强了胰岛素分子本身的作用，糖原沉积增加、丙酮酸激酶（PK）诱导增加以及磷酸烯醇式丙酮酸羧激酶（PEP-CK）活性降低都证明了这一点。然而，细胞暴露于相对高剂量的胰岛素和PCMBS具有破坏性，糖原水平降低证明了这一点，这很可能是胰岛素受体过度刺激和代谢应激的结果。因此，SH阻断化合物能够触发胰岛素依赖性代谢过程。相对不易渗透的有机汞PCMBS被证明是最有效的胰岛素模拟SH阻断化合物。
