Effects of phorbol esters on insulin receptor function and insulin action in hepatocytes: evidence for heterogeneity.
We investigated the effect of phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator on insulin receptors and insulin action in freshly isolated and primary cultures of rat hepatocytes. PMA (1 x 10(-7) M) did not alter insulin receptor numbers or affinity either acutely or chronically but within 60 minute inactivated insulin stimulated tyrosine kinase of the insulin receptor. PKC activation inhibited insulin (1 x 10(-7) M) stimulation of glycogen and lipid synthesis with a decrease or no change in basal glycogenesis and lipogenesis respectively. However, PKC activation did not alter insulin stimulated or basal amino acid transport even though PKC activation inhibited insulin stimulation of the insulin receptor tyrosine kinase. Thus, within one tissue, PKC activation has differential effect on insulin action depending on which pathway is examined. Furthermore, insulin stimulation of the insulin receptor tyrosine kinase may not be a necessary step for all insulin signaling pathways.
Caro
J F
JF
Department of Medicine, School of Medicine, East Carolina University, Greenville, NC 27858-4354.
Jenquin
M
M
Long
S
S
D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology* / Q000502:physiology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D011493:Protein Kinase C / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate