Insulin action on cardiac glucose transport: studies on the role of protein kinase C.
Isolated ventricular cardiomyocytes from adult rat have been used to elucidate a possible relationship between protein kinase C (PKC) and the stimulatory action of insulin on cardiac glucose transport. Cells were incubated in the presence of either insulin or phospholipase C from Clostridium perfringens (PLC-Cp) and intracellular sn-1,2-diacylglycerol (DAG) levels and initial rates of 3-O-methylglucose transport were determined. Insulin had no effect on the DAG mass level, whereas it was elevated by PLC-Cp to 200% of control. Under these conditions the hormone produced a 2.7-fold stimulation of glucose transport with no significant effect of PLC-Cp. Insulin was unable to produce a redistribution of PKC, whereas phorbol 12-myristate 13-acetate (PMA) increased membrane associated PKC twofold. The PKC inhibitors tamoxifen and staurosporine did not interfere with glucose transport stimulation by insulin. Furthermore, cells treated with PMA exhibited unaltered basal and maximally insulin stimulated rates of glucose transport. In contrast, at physiological concentrations of insulin the stimulatory action of the hormone was significantly reduced. We conclude from our data that PKC is not involved in insulin action on cardiac glucose transport. However, activation of this enzyme may lead to a modified insulin sensitivity of the cardiac cell.
Laboratory of Molecular Cardiology, Diabetes Research Institute, Düsseldorf, Germany.
M
M
Russ
J
J
Eckel
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004075:Diglycerides / Q000032:analysis; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
C011439:1,2-diacylglycerol; D004075:Diglycerides; D007328:Insulin; D011493:Protein Kinase C; D005947:Glucose