Long-term exposure of INS-1 cells to cis and trans fatty acids influences insulin release and fatty acid oxidation differentially
Long-term exposure of INS-1 cells to cis and trans fatty acids influences insulin release and fatty acid oxidation differentially
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DOI：
10.1016/j.metabol.2004.02.026
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发表时间：
2004-09-01
影响因子：
9.8
通讯作者：
Hermansen, K
中科院分区：
文献类型：
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作者：
Alstrup, KK;Brock, B;Hermansen, K
已经确定了脂肪酸水平升高在2型糖尿病中存在的β细胞功能恶化的发病机制中的重要性。β细胞长期暴露于高水平的脂肪酸会导致低葡萄糖时胰岛素分泌增强（基础胰岛素释放），而葡萄糖刺激的胰岛素分泌（GSIS）减少或不变。我们先前已经证明，脂肪酸（顺式和反式异构体）的空间构型对β细胞功能的急性影响是重要的。在这项研究中，我们的目的是阐明长期暴露后空间配置是否也影响β细胞功能。因此，我们比较了INS-1细胞与顺式（顺式C 18：1-11）和反式异油酸（反式C 18：1 - 11）以及油酸（顺式C 18：1-9）和反式油酸（反式C 18：1-9）培养3天对基础和葡萄糖刺激的胰岛素释放的影响。所有的脂肪酸测试增加基础胰岛素释放，但是，一个显着较低的基础胰岛素释放被证明与0.3至0.4 mmol/L的反式异油酸相比，等摩尔水平的顺式异构体培养的细胞。顺式或反式异油酸或油酸对GSIS无明显影响，而0.3 ~ 0.4mmol/L的反油酸对GSIS有刺激作用。脂肪酸诱导的13种细胞变化背后的机制与葡萄糖和脂肪酸氧化的变化有关。我们证明了在长期暴露于所有测试的脂肪酸后，13个细胞中的脂肪酸氧化增加。有趣的是，两种反式异构体（反式异油酸和反式油酸）诱导的脂肪酸氧化比顺式异构体（顺式异油酸和油酸，分别）。当INS-1细胞与任一种脂肪酸一起培养时，未发现葡萄糖氧化的变化。脂肪酸氧化程度的增加与肉毒碱棕榈酰转移酶I（CPT-I）mRNA含量的增加有关，但不同脂肪酸对CPT-I mRNA含量的影响无差异，β细胞胰岛素mRNA表达不受脂肪酸的影响。总之，我们已经证明，胰岛素分泌的病理变化从INS-1细胞长期培养的脂肪酸水平升高更明显的顺式（顺式异油酸和油酸），而不是反式异构体（反式异油酸和反式油酸）。我们认为，这至少在一定程度上，可以解释为一个较低的脂肪酸氧化与反式脂肪酸异构体相比，顺式培养的细胞。显然，脂肪酸氧化的差异不是由CPT-Ⅰ mRNA诱导增加引起的，也不是由长期暴露于脂肪酸的13个细胞中葡萄糖氧化或胰岛素mRNA的变化引起的。(C)2004年爱思唯尔公司All rights reserved.
The importance of elevated levels of fatty acids in the pathogenesis of the deteriorated beta-cell function present in type 2 diabetes has been established. Long-term exposure of the beta-cell to high levels of fatty acids causes enhanced insulin secretion at low glucose (basal insulin release), while glucose-stimulated insulin secretion (GSIS) is decreased or unchanged. We have previously demonstrated that the spatial configuration of fatty acids (cis and trans isomers) is of importance for the acute impact on the beta-cell function. In this study we aimed to elucidate whether the spatial configuration also influenced beta-cell function after long-term exposure. Thus, we compared the effect of 3 days culture of INS-1 cells with cis (cis C 18:1-11) and trans vaccenic acid (trans C 18:1-11), as well as oleic (cis C 18:1-9) and elaidic acid (trans C 18:1-9), on basal and glucose-stimulated insulin release. All fatty acids tested increased basal insulin release; however, a significantly lower basal insulin release was demonstrated for cells cultured with 0.3 to 0.4 mmol/L trans vaccenic acid compared to equimolar levels of the cis isomer. GSIS was not changed by cis or trans vaccenic acid or by oleic acid, whereas it was stimulated by 0.3 to 0.4 mmol/L elaidic acid. The mechanisms behind the fatty acid-induced changes in the 13 cells have been linked to changes in glucose and fatty acid oxidation. We demonstrated an increased fatty acid oxidation in 13 cells after long-term exposure to all of the tested fatty acids. Interestingly, both trans isomers (trans vaccenic and elaidic acid) induced higher fatty acid oxidation than the cis isomers (cis vaccenic and oleic acid, respectively). No changes in glucose oxidation were found when INS-1 cells were cultured with either of the fatty acids. The increased fatty acid oxidation was associated with an increased content of carnitine palmitoyltransferase I (CPT-I) mRNA, but no difference in the content of CPT-I mRNA to the different fatty acids was found. Insulin mRNA expression in beta cells was not affected by the fatty acids. In conclusion, we have demonstrated that the pathological changes in insulin secretion from INS-1 cells to long-term culture with elevated levels of fatty acids are more pronounced for the cis (cis vaccenic acid and oleic acid) rather than the trans isomers (trans vaccenic acid and elaidic acid). We suggest that this, at least in part, may be explained by a lower fatty acid oxidation in cells cultured with the cis compared to the trans fatty acid isomers. Apparently, the difference in fatty acid oxidation was not caused by an increased induction of CPT-I mRNA, nor by changes in glucose oxidation or insulin mRNA in 13 cells chronically exposed to the fatty acids. (C) 2004 Elsevier Inc. All rights reserved.