title: Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells.
abstract: An increase in circulating levels of specific NEFAs (non-esterified fatty acids) has been implicated in the pathogenesis of insulin resistance and impaired glucose disposal in skeletal muscle. In particular, elevation of SFAs (saturated fatty acids), such as palmitate, has been correlated with reduced insulin sensitivity, whereas an increase in certain MUFAs and PUFAs (mono- and poly-unsaturated fatty acids respectively) has been suggested to improve glycaemic control, although the underlying mechanisms remain unclear. In the present study, we compare the effects of palmitoleate (a MUFA) and palmitate (a SFA) on insulin action and glucose utilization in rat L6 skeletal muscle cells. Basal glucose uptake was enhanced approx. 2-fold following treatment of cells with palmitoleate. The MUFA-induced increase in glucose transport led to an associated rise in glucose oxidation and glycogen synthesis, which could not be attributed to activation of signalling proteins normally modulated by stimuli such as insulin, nutrients or cell stress. Moreover, although the MUFA-induced increase in glucose uptake was slow in onset, it was not dependent upon protein synthesis, but did, nevertheless, involve an increase in the plasma membrane abundance of GLUT1 and GLUT4. In contrast, palmitate caused a substantial reduction in insulin signalling and insulin-stimulated glucose transport, but was unable to antagonize the increase in transport elicited by palmitoleate. Our findings indicate that SFAs and MUFAs exert distinct effects upon insulin signalling and glucose uptake in L6 muscle cells and suggest that a diet enriched with MUFAs may facilitate uptake and utilization of glucose in normal and insulin-resistant skeletal muscle.
authors.affiliation: Division of Molecular Physiology, Centre for Interdisciplinary Research, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Dimopoulos
authors.forename: Maria
authors.initials: M
authors.lastname: Watson
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Harinder S
authors.initials: HS
authors.lastname: Hundal
mesh_terms: D026924:Amino Acid Transport System A; D026905:Amino Acid Transport Systems / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016895:Culture Media, Serum-Free; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008954:Models, Biological; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis; D019301:Oleic Acid / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D026924:Amino Acid Transport System A; D026905:Amino Acid Transport Systems; D000596:Amino Acids; D000621:Aminoisobutyric Acids; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009124:Muscle Proteins; D011500:Protein Synthesis Inhibitors; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; C412568:Slc38a2 protein, rat; C008757:palmitoleic acid; C017911:2-(methylamino)isobutyric acid; D019301:Oleic Acid; D019308:Palmitic Acid; D006003:Glycogen; D003513:Cycloheximide; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D038362:Glycogen Synthase Kinase 3; D005947:Glucose