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Oleate protects against palmitate-induced insulin resistance in L6 myotubes

  • Dan Gao (a1), Helen R. Griffiths (a1) and Clifford J. Bailey (a1)
  • DOI:
  • Published online: 22 July 2009

Oleate has been shown to protect against palmitate-induced insulin resistance. The present study investigates mechanisms involved in the interaction between oleate and palmitate on insulin-stimulated glucose uptake by L6 skeletal muscle cells. L6 myotubes were cultured for 6 h with palmitate or oleate alone, and combinations of palmitate with oleate, with and without phosphatidylinositol 3-kinase (PI3-kinase) inhibition. Insulin-stimulated glucose uptake, measured by uptake of 2-deoxy-d-[3H]glucose, was almost completely prevented by 300 μm-palmitate. Cells incubated with oleate up to 750 μmol/l maintained a significant increase in insulin-stimulated glucose uptake. Co-incubation of 50–300 μm-oleate with 300 μm-palmitate partially prevented the decrease in insulin-stimulated glucose uptake associated with palmitate. Adding the PI3-kinase inhibitors wortmannin (10− 7 mol/l) or LY294002 (25 μmol/l) to 50 μm-oleate plus 300 μm-palmitate significantly reduced the beneficial effect of oleate against palmitate-induced insulin resistance, indicating that activation of PI3-kinase is involved in the protective effect of oleate. Thus, the prevention of palmitate-induced insulin resistance by oleate in L6 muscle cells is associated with the ability of oleate to maintain insulin signalling through PI3-kinase.

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*Corresponding author: Dr Helen R. Griffiths, fax +44 121 359 0572, email
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1AH Mokdad , ES Ford , BA Bowman , (2003) Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289, 7679.

2SE Kahn , RL Hull & KM Utzscheider (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840846.

3SA Ritchie & JMC Connell (2007) The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis 17, 319326.

5GI Shulman (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106, 171175.

6JD McGarry (2002) Banting lecture: 2001: dysregulation of fatty acid metabolism in the aetiology of type 2 diabetes. Diabetes 51, 718.

7 M Roden , TB Price , G Perseghin , (1996) Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 97, 28592865.

8A Dresner , D Laurent , M Marcucci , (1998) Effects of free fatty acids on glucose transport and IRS1-associated phophatidylinositol 3-kinase activity. J Clin Invest 103, 253259.

9YT Kruszynska , DS Worrall , J Ofrecio , (2002) Fatty acid-induced insulin resistance: decreased muscle PI3K activation but unchanged Akt phosphorylation. J Clin Endocrinol Metab 87, 226234.

10JS Lee , SK Pinnamaneni , SJ Eo , (2006) Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J Appl Physiol 100, 14671474.

11M Van Epps-Fung , J Williford , A Wells , (1997) Fatty acid-induced insulin resistance in adipocytes. Endocrinology 138, 43384345.

12 JA Chavez & SA Summers (2003) Characterizing the effects of saturated fatty acids on insulin signalling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes. Arch Biochem Biophys 419, 101109.

13MA Sabin , CE Stewart , EC Crowne , (2007) Fatty acid-induced defects in insulin signalling, in myotubes derived from children, are related to ceramide production from palmitate rather than the accumulation of intramyocellular lipid. J Cell Physiol 211, 244252.

15 T Coll , E Eyre , R Rodriguez-Calvo , (2008) Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells. J Biol Chem 283, 1110711116.

16CJ Bailey , SL Turner , SH Bates , (2001) Sibutramine metabolites increase glucose transport by cultured rat muscle cells. Int J Obes Relat Metab Disord 25, 478485.

17 WY Zhang , E Schwartz , YJ Wang , (2006) Elevated concentrations of nonesterified fatty acids increase monocyte expression of CD11b and adhesion to endothelial cells. Arterioscler Thromb Vasc Biol 26, 514519.

19CJ Bailey & SL Turner (2004) Glucosamine-induced insulin resistance in L6 muscle cells. Diabetes Obes Metab 6, 293298.

20DW Nicholson , A Ali , NA Thornberry , (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376, 37 − 43.

21 PK Smith , RI Krohn , GT Hermanson , (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150, 7685.

22A Toker & CL Cantley (1997) Signalling through the lipid products of phosphoinositide-3-OH kinase. Nature 387, 673676.

23S Sinha , G Perdomo , NF Brown , (2004) Fatty acid-induced insulin resistance in L6 myotubes is prevented by inhibition of activation and nuclear localization of nuclear factor κB. J Biol Chem 279, 4129441301.

24G Boden , X Chen , J Ruiz , (1994) Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 93, 24232446.

25RN Kolesnick & M Krönke (1998) Regulation of ceramide production and apoptosis. Annu Rev Physiol 60, 643665.

26E Hajduch , A Balendran , IH Batty , (2001) Ceramide impairs the insulin-dependent membrane recruitment of protein kinase B leading to a loss of downstream signalling in L6 skeletal muscle cells. Diabetologia 44, 173183.

27SA Summers , LA Garza , H Zhou , (1998) Regulation of insulin-stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide. Mol Cell Biol 18, 54575464.

28 C Schmitz-Peiffer , DL Craig & TJ Biden (1999) Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. J Biol Chem 274, 2420224210.

29 JA Chavez , TA Knotts , LP Wang , (2003) A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem 278, 1029710303.

30 D Powell , S Turban , A Gray , (2004) Intracellular ceramide synthesis and protein kinase Cζ activation play an essential role in palmitate-induced insulin resistance in rat L6 skeletal muscle cells. Biochem J 382, 619629.

31 SI Itani , NB Ruderman , F Schmieder , (2002) Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α. Diabetes 51, 20052011.

32ME Griffin , MJ Marcucci , GW Cline , (1999) Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signalling cascade. Diabetes 48, 12701274.

33HKR Karlsson & JR Zierath (2007) Insulin signalling and glucose transport in insulin resistant human skeletal muscle. Cell Biochem Biophys 48, 103113.

35JK Kim , JJ Fillmore , MJ Sunshine , (2004) PKC-θ knockout mice are protected from fat-induced insulin resistance. J Clin Invest 114, 823827.

36M Massaro , MA Carluccio , A Paolicchi , (2002) Mechanisms for reduction of endothelial activity by oleate: inhibition of nuclear factor-κB through antioxidant effects. Prostaglandins Leukot Essent Fatty Acids 67, 175181.

37 PJ Voshol , MC Jong , VE Dahlmans , (2001) In muscle-specific lipoprotein lipase-overexpressing mice, muscle triglyceride content is increased without inhibition of insulin-stimulated whole-body and muscle-specific glucose uptake. Diabetes 50, 25852590.

39 LL Listenberger , XL Han , SE Lewis , (2003) Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A 100, 30773082.

40DE Kelly , J He , EV Menshikova , (2002) Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51, 29442950.

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