Effects of sulphydryl reagents on receptor-mediated hormonal responses at the cellular level: insulin-mimicking characteristics of thiol-blocking compounds in rat hepatocyte primary cultures.
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.
Boot
J H
JH
Department Veterinary Pharmacology, Pharmacy and Toxicology, Utrecht, The Netherlands.
D000818:Animals; D002478:Cells, Cultured; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D007328:Insulin; D008112:Liver Glycogen; D013439:Sulfhydryl Reagents; D006006:Glycogen Synthase; D011770:Pyruvate Kinase; D011972:Receptor, Insulin; D010729:Phosphoenolpyruvate Carboxykinase (GTP)