Arachidonic acid inhibition of insulin action and phosphoinositide turnover in fat cells.
Incubation of isolated rat adipocytes with 1 microM arachidonic acid (20:4) coupled to equimolar amounts of bovine serum albumin (BSA) results in the cellular uptake of the fatty acid and a subsequent inhibition of insulin-stimulated antilipolysis and lipogenesis without altering glucose transport. These effects are apparently not mediated at the insulin receptor level since insulin binding is not altered in arachidonate-enriched fat cells. In addition, effects on antilipolytic and lipogenic are not specific for arachidonic acid. Oleic or palmitic acid can mimic these effects in both insulin-stimulated and PGE2-stimulated cells. Adipocyte enrichment with 20:4, however, specifically inhibits the insulin-stimulated turnover of phosphoinositides. The latter can be specifically prevented by preincubation with ibuprofen. These results suggest that the level of intracellular arachidonate may play a major role in modulating insulin-stimulated phosphoinositide turnover and thereby indirectly regulate certain aspects of insulin action which involve lipid metabolism.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D015232:Dinoprostone; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D001095:Arachidonic Acids; D007328:Insulin; D008055:Lipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D011458:Prostaglandins E; C037178:phosphatidylinositol 4-phosphate; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D005947:Glucose; D015232:Dinoprostone; D004837:Epinephrine