Attenuation of insulin actions in primary rat hepatocyte cultures by phenylarsine oxide.
Phenylarsine oxide (PAO), a trivalent arsenical which complexes vicinal dithiols, prevented the action of insulin in primary cultured adult rat hepatocytes. Simultaneous short-term treatment of 48-h old cells with insulin and 2 microM PAO resulted in complete attenuation of the insulin-dependent increase in the level of fructose 2,6-bisphosphate and the activation of phosphofructokinase 2, pyruvate kinase, glucokinase flux and glycolysis. Basal rates of glucose transport and glycolysis were not affected. PAO also abolished stimulation of glycogen synthesis and amino-acid transport and the decrease of glycogenolysis evoked by insulin. The 20-fold activation of the insulin receptor tyrosine kinase by insulin was, however, not reduced by PAO. The data suggest that in differentiated hepatocytes insulin signal transduction involves vicinal sulhydryls located at a post-receptor step.
Quentmeier
A
A
Institut für Biochemie, Fachbereich Medizin, Georg-August-Universität Göttingen.
Klein
H
H
Unthan-Fechner
K
K
Probst
I
I
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D005635:Fructosediphosphates / Q000378:metabolism; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010732:Phosphofructokinase-1 / Q000378:metabolism; D010766:Phosphorylation; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000596:Amino Acids; D001152:Arsenicals; D005635:Fructosediphosphates; D007328:Insulin; C029341:oxophenylarsine; C027652:fructose 2,6-diphosphate; D006003:Glycogen; D010732:Phosphofructokinase-1; D005941:Glucokinase; D011770:Pyruvate Kinase; D011972:Receptor, Insulin; D005947:Glucose