title: Phosphatidylinositol 3-kinase-dependent insulin regulation of long-chain fatty acid (LCFA) metabolism in L6 muscle cells: involvement of atypical protein kinase C-zeta in LCFA uptake but not oxidation.
abstract: Insulin is important in the regulation of muscle metabolism. However, its role in the regulation of muscle long-chain fatty acid (LCFA) metabolism, independent of glucose, is not clear. To determine whether insulin regulates LCFA metabolism independent of glucose and if so, via which signaling pathway, L6 myotubes were incubated, in the presence or absence of insulin (100 nM) and with either an inhibitor of phosphatidylinositol 3-kinase (PI3K) (wortmannin (W), 50 nM), protein kinase B (PKB)/Akt (A, 10 muM), or atypical protein kinase C-zeta (aPKC-zeta) (mP, 100 muM). LCFA kinetic parameters were measured via incubation with [1-(14)C]palmitate. Basal LCFA uptake was found to increase linearly with time (1-60 min) and concentration (50-750 muM). LCFA uptake increased in the presence of insulin and was maximum at 10 nM (P<0.05). Wortmannin prevented the insulin-induced increase in LCFA uptake and decrease in LCFA oxidation. While mP abolished the insulin-induced increase in LCFA uptake, it did not prevent the insulin-induced decrease in LCFA oxidation. None of the variables were affected by Akt inhibition. These results suggest a direct effect of insulin on LCFA metabolism in muscle cells, and that downstream of PI3K, aPKC-zeta, but not PKB/Akt mediates the effects of insulin on LCFA uptake but not oxidation.
authors.affiliation: Department of Kinesiology and Biological Sciences, College of Letters, Arts, and Sciences, University of Southern California, 3560 Watt Way, PED 107, Los Angeles, California 90089-0652, USA.
authors.forename: Karen R
authors.initials: KR
authors.lastname: Kelly
authors.forename: Chin K
authors.initials: CK
authors.lastname: Sung
authors.forename: Marcia J
authors.initials: MJ
authors.lastname: Abbott
authors.forename: Lorraine P
authors.initials: LP
authors.lastname: Turcotte
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007329:Insulin Antagonists / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010168:Palmitates / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D000077191:Wortmannin; D000099221:Protein Kinase C zeta
chemical_list: D000730:Androstadienes; D005227:Fatty Acids; D005947:Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D007329:Insulin Antagonists; D010168:Palmitates; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D000077191:Wortmannin; D000099221:Protein Kinase C zeta