Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells
Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells
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DOI：
10.1042/bj20060244
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发表时间：
2006-11-01
影响因子：
4.1
通讯作者：
Hundal, Harinder S.
中科院分区：
文献类型：
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作者：
Dimopoulos, Nikolaos;Watson, Maria;Hundal, Harinder S.
循环中特定NEFAs(非酯化脂肪酸)水平的增加与胰岛素抵抗和骨骼肌糖代谢受损的发病机制有关。特别是，饱和脂肪酸(如棕榈酸)的增加与胰岛素敏感性的降低有关，而某些MUFAs和PUFAs(分别是单不饱和脂肪酸和多不饱和脂肪酸)的增加被认为可以改善血糖控制，尽管潜在的机制尚不清楚。在本研究中，我们比较了棕榈酸酯(A MUFA)和棕榈酸酯(A SFA)对大鼠L6骨骼肌细胞胰岛素作用和葡萄糖利用的影响。基础葡萄糖摄取量约有增加。用棕榈酸酯处理细胞后增加2倍。MUFA诱导的葡萄糖转运增加导致葡萄糖氧化和糖原合成的相关增加，这不能归因于通常受胰岛素、营养物质或细胞应激等刺激调节的信号蛋白的激活。此外，尽管MUFA诱导的葡萄糖摄取增加开始较慢，但它不依赖于蛋白质合成，但确实涉及GLUT1和GLUT4质膜丰度的增加。相反，棕榈酸酯导致胰岛素信号和胰岛素刺激的葡萄糖转运显著减少，但不能拮抗棕榈酸酯引起的转运增加。我们的发现表明，SFAs和MUFAs对L6肌细胞的胰岛素信号和葡萄糖摄取有明显的影响，并提示富含MUFAs的饮食可能促进正常和胰岛素抵抗骨骼肌对葡萄糖的吸收和利用。
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.