Oleate protects against palmitate-induced insulin resistance in L6 myotubes

School of Life and Health Sciences, Aston University, Birmingham, UK.
The British journal of nutrition (Impact Factor: 3.45). 08/2009; 102(11):1557-63. DOI: 10.1017/S0007114509990948
Source: PubMed


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 microm-palmitate. Cells incubated with oleate up to 750 micromol/l maintained a significant increase in insulin-stimulated glucose uptake. Co-incubation of 50-300 microm-oleate with 300 microm-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 micromol/l) to 50 microm-oleate plus 300 microm-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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Available from: Helen R Griffiths, Jan 15, 2014
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    • "Palmitate and palmitoleate have distinct direct effects upon insulin-stimulated glucose disposal in L6 myotubes (Dimopoulos et al., 2006), but the effects of palmitoleate were not shown to be mediated through a protective effect on insulin signalling previously . However, others have shown that oleate protects against the effects of palmitate by reducing the impairment in PI3K signalling (Coll et al., 2008; Gao et al., 2009) and through anti-inflammatory effects (Coll et al., 2008), including prevention of MAPK activation (Kadotani et al., 2009). This is likely mediated through reduced synthesis of ceramide and/or diacylglycerol in palmitate-treated myotubes (Chavez and Summers, 2003), rather than accumulation of the more inert triacylglycerol and this mechanism may also result in increased pro-inflammatory cytokine production by macrophages (Schilling et al., 2013). "
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    • "Furthermore, treatment with antioxidants prevented the development of insulin resistance in both cell culture and ex vivo experimental models [15,16,18]. Antioxidants also partially prevented cellular insulin resistance caused by tumor necrosis factor-alpha (TNFα), glucocorticoids, and the saturated fatty acid palmitic acid, suggesting that oxidative stress plays a key role in their action on glucose metabolism [19,20]. Together, these data show that oxidative stress can both directly and indirectly inhibit glucose metabolism. "
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    • "One of the major sites for SFA-mediated adverse function is INSR [70]. In contrast, OA improves insulin signaling and protects against PA-induced insulin resistance in L6 myotubes [71]. We also observed that OA upregulated INSR mRNA expression in glycolytic muscle and did not significantly alter the circulating glucose/insulin balance, which indicates enhanced insulin sensitivity. "
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