Insulin antagonizes epinephrine activation of the membrane transport of fatty acids. Potential site for hormonal suppression of lipid mobilization.
Membrane transport of long chain fatty acids in the isolated rat adipocyte can be strongly stimulated by epinephrine (Abumrad, N. A., Perry, P. R., and Whitesell, R. R. (1985) J. Biol. Chem. 260, 9969-9971). We now report that insulin at physiological concentrations can completely block or reverse the epinephrine effect. Insulin was optimally effective at a concentration of about 0.1 nM in inhibiting transport activation by 0.3 and 3 microM epinephrine (0.1 and 1.0 microgram/ml). High concentrations of insulin (above 1 nM) were generally less effective and this was particularly true at the highest dose of epinephrine (1.0 microgram/ml). The insulin effect was shown to be on the transport process since insulin inhibited epinephrine activation of transport in both directions (influx and efflux). No effect of insulin on basal transport was observed over a wide range of concentrations (0.01-10 nM). Insulin's antagonism of transport activation by epinephrine appeared dependent on ATP metabolism since it was abolished by preincubating the cells with dinitrophenol (1 mM). Dinitrophenol, however, could not reverse the insulin effect when exposure to the hormone preceded that to dinitrophenol, consistent with an action of insulin at the transport step. The data indicate that regulation of the membrane transport of fatty acids is a potential site for insulin's action to suppress lipid mobilization.
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004140:Dinitrophenols; D005227:Fatty Acids; D007328:Insulin; D009829:Oleic Acids; D019301:Oleic Acid; D004837:Epinephrine