Rapid effects of phorbol esters on isolated rat adipocytes. Relationship to the action of protein kinase C.
Treatment of isolated rat adipocytes with tumor-promoting phorbol esters, caused a fivefold stimulation of glucose oxidation, determined as 14CO2 production from [1-14C]glucose and a fivefold increase in the rate of lipid synthesis from [14C]glucose. Treatment of the cells with 12-O-tetradecanoylphorbol 13-acetate increased the rate of 86Rb+ uptake into the cells. Also phospholipase C was able to stimulate the rate of glucose oxidation; phospholipase C and 12-O-tetradecanoylphorbol 13-acetate stimulated glucose oxidation in a non-synergistic fashion, indicating a common mechanism for their action. Active phorbol esters and, in part, also phospholipase C, caused a translocation of protein kinase C activity from the soluble to the particulate fraction of the adipocytes. This process was rapid, being complete 30 s after the addition of phorbol ester, and resulted in the appearance of the kinase mainly in the mitochondrial and plasma membrane fractions. A comparison between the binding characteristics of adipocyte protein kinase C and the metabolic effects of the phorbol esters on the adipocytes revealed that the dose-response relationship did not correlate with binding of the phorbol esters, but, rather, a correlation was observed between the dose of phorbol esters required for translocation of protein kinase C and the intracellular effects. The results indicate that the intracellular translocation of protein kinase C might be a trigger for the effects of phorbol esters on the adipocyte and that binding of the esters to protein kinase C is not a sufficient event to cause this effect. Furthermore, it is suggested that activation of protein kinase C might be partly the action of hormones, such as insulin, on the fat cells.
Skoglund
G
G
Hansson
A
A
Ingelman-Sundberg
M
M
D000273:Adipose Tissue / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000201:enzymology; D005947:Glucose / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis; D008928:Mitochondria / Q000201:enzymology; D010084:Oxidation-Reduction / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D014178:Translocation, Genetic / Q000187:drug effects; D010738:Type C Phospholipases / Q000494:pharmacology
D008055:Lipids; D010703:Phorbol Esters; D010704:Phorbols; D011494:Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D005947:Glucose