Sensitivity of adipocyte basal and insulin-stimulated hexose transport to the membrane lipid structure.
A series of anesthetic alcohols inhibited basal and insulin-stimulated 2-deoxy-D-[1-14C]glucose transport in adipocytes over total alcohol concentration ranges that cause local anesthesia of rat sciatic nerve. The relative potencies of the inhibition caused by the alcohols increased in the following order: methanol less than ethanol less than propanol less than butanol less than benzyl alcohol less than hexanol less than octanol. The inhibition was reversible and correlated well with the known partitioning of the alcohols into lipids of biological membranes. Adipocyte membranes were labeled with the 5-nitroxide stearate spin probe to investigate the effects of the alcohols on the dynamic structure of membrane lipids of the adipocyte. The alcohols increased the membrane "fluidity", and the relative concentration dependence of the effects closely paralleled that noted from methanol to octanol in transport studies. Alcohols from methanol to hexanol caused inhibition of hexose transport at molar potencies comparable to that observed for membrane disordering. This suggests that hydrophobic regions of the transporter and its lipid environment are perturbed by a comparable mechanism for each alcohol. The cholesterol-complexing polyene antibiotic filipin inhibited hexose transport and influenced the mobility of lipid domains sampled with the nitroxide cholestane, cholesterol-like spin probe. The data are consistent with the concept that the membrane structural/functional effects are mediated by formation of 1:1 cholesterol:filipin complexes. Alcohols and filipin inhibited inherent transporter activity and perturbed the membrane lipid structure without dramatically diminishing transport stimulation by insulin above basal. The specific organization of membrane lipids (particularly cholesterol) may provide an essential environment for optimal transport system activity.
D000273:Adipose Tissue / Q000378:metabolism*; D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D005372:Filipin / Q000494:pharmacology*; D006601:Hexoses / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000502:physiology*; D011090:Polyenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000438:Alcohols; D006601:Hexoses; D007328:Insulin; D008563:Membrane Lipids; D011090:Polyenes; D005372:Filipin