Phorbol ester provokes insulin-like effects on glucose transport, amino acid uptake, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes.
We evaluated the possibility that diacylglycerol may function as a second messenger in insulin action. To this end, we employed 12-O-tetradecanoyl phorbol 13-acetate (TPA) to mimic diacylglycerol in BC3H-1 myocytes. Like insulin, TPA provoked rapid increases in 2-deoxyglucose transport and pyruvate dehydrogenase activity in mature insulin-responsive BC3H-1 cultured myocytes. TPA also stimulated amino acid uptake, as evidenced by uptake of alpha-methylaminoisobutyric acid; the relatively slow time course of this effect paralleled that of insulin. In contrast, the effects of TPA were not apparent in undifferentiated BC3H-1 myoblasts, which were also unresponsive to insulin. The insulin-like effects in the myocytes appeared to be specific for TPA, the biologically active phorbol diester which activates protein kinase C, as other tested phorbol derivatives were without effect. Effects of maximally effective concentrations of TPA and insulin were nonadditive. Two synthetic diacylglycerols, 1,2-diolien and 1-oleoyl-2-acetyl-sn-glycerol, also provoked insulin-like effects on 2-deoxyglucose transport. Since insulin rapidly increases diacylglycerol levels in these cells, and TPA mimics diacylglycerol biochemically, it is possible that insulin may control cellular processes through changes in diacylglycerol.
Farese
R V
RV
Standaert
M L
ML
Barnes
D E
DE
Davis
J S
JS
Pollet
R J
RJ
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000032:analysis; D011768:Pyruvate Dehydrogenase Complex / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000596:Amino Acids; D004075:Diglycerides; D007328:Insulin; D010704:Phorbols; D011768:Pyruvate Dehydrogenase Complex; D011494:Protein Kinases; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate