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Palmitate and oleate modify membrane fluidity and kinase activities of INS-1E β-cells alongside altered metabolism-secretion coupling.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2019-12-07 , DOI: 10.1016/j.bbamcr.2019.118619 Lucie Oberhauser 1 , Sabrina Granziera 1 , Adai Colom 2 , Antoine Goujon 3 , Vanessa Lavallard 4 , Stefan Matile 3 , Aurélien Roux 2 , Thierry Brun 1 , Pierre Maechler 1
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2019-12-07 , DOI: 10.1016/j.bbamcr.2019.118619 Lucie Oberhauser 1 , Sabrina Granziera 1 , Adai Colom 2 , Antoine Goujon 3 , Vanessa Lavallard 4 , Stefan Matile 3 , Aurélien Roux 2 , Thierry Brun 1 , Pierre Maechler 1
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Chronic exposure to elevated levels of glucose and free fatty acids impairs beta-cell function, leading to insulin secretion defects and eventually beta-cell failure. Using a semi-high throughput approach applied to INS-1E beta-cells, we tested multiple conditions of chronic exposure to basal, intermediate and high glucose, combined with saturated versus mono- and polyunsaturated fatty acids in order to assess cell integrity, lipid metabolism, mitochondrial function, glucose-stimulated calcium rise and secretory kinetics. INS-1E beta-cells were cultured for 3 days at different glucose concentrations (5.5, 11.1, 25 mM) without or with BSA-complexed 0.4 mM saturated (C16:0 palmitate), monounsaturated (C18:1 oleate) or polyunsaturated (C18:2 linoleate, C18:3 linolenate) fatty acids, resulting in 0.1-0.5 μM unbound fatty acids. Accumulation of triglycerides in cells exposed to fatty acids was glucose-dependent, oleate inducing the strongest lipid storage and protecting against glucose-induced cytotoxicity. The combined chronic exposure to both high glucose and either palmitate or oleate altered mitochondrial function as well as glucose-induced calcium rise. This pattern did not directly translate at the secretory level since palmitate and oleate exhibited distinct effects on the first and the second phases of glucose-stimulated exocytosis. Both fatty acids changed the activity of kinases, such as the MODY-associated BLK. Additionally, chronic exposure to fatty acids modified membrane physicochemical properties by increasing membrane fluidity, oleate exhibiting larger effects compared to palmitate. Chronic fatty acids differentially and specifically exacerbated some of the glucotoxic effects, without promoting cytotoxicity on their own. Each of the tested fatty acids functionally modified INS-1E beta-cell, oleate inducing the strongest effects.
中文翻译：
棕榈酸酯和油酸酯改变了INS-1Eβ细胞的膜流动性和激酶活性，同时改变了新陈代谢-分泌耦合。
长期暴露于高水平的葡萄糖和游离脂肪酸会损害β细胞功能，导致胰岛素分泌缺陷，最终导致β细胞衰竭。我们使用适用于INS-1Eβ细胞的半高通量方法，测试了长期暴露于基础，中等和高葡萄糖的多种情况，并结合了饱和脂肪酸与单不饱和脂肪酸和多不饱和脂肪酸，以评估细胞完整性，脂质代谢，线粒体功能，葡萄糖刺激的钙升高和分泌动力学。INS-1E beta细胞在不同的葡萄糖浓度（5.5、11.1、25 mM）下培养3天，无或有BSA复合的0.4 mM饱和（C16：0棕榈酸酯），单不饱和（C18：1油酸酯）或多不饱和（C18） ：2亚油酸酯，C18：3亚油酸酯）脂肪酸，产生0.1-0.5μM的未结合脂肪酸。暴露于脂肪酸的细胞中甘油三酸酯的积累是葡萄糖依赖性的，油酸酯可诱导最强的脂质储存并防止葡萄糖诱导的细胞毒性。长期暴露于高葡萄糖和棕榈酸酯或油酸酯的综合长期暴露会改变线粒体功能以及葡萄糖诱导的钙升高。由于棕榈酸酯和油酸酯对葡萄糖刺激的胞吐作用的第一和第二阶段表现出不同的作用，因此该模式在分泌水平上不直接翻译。两种脂肪酸都改变了激酶的活性，例如与MODY相关的BLK。另外，与棕榈酸酯相比，长期暴露于脂肪酸可通过增加膜流动性来改变膜的理化性质，油酸酯表现出更大的作用。慢性脂肪酸差异性地且特异性地加剧了某些糖毒作用，而没有自身促进细胞毒作用。每个测试的脂肪酸功能性地修饰了INS-1Eβ细胞，油酸酯诱导最强的作用。
更新日期：2019-12-07
中文翻译：
棕榈酸酯和油酸酯改变了INS-1Eβ细胞的膜流动性和激酶活性，同时改变了新陈代谢-分泌耦合。
长期暴露于高水平的葡萄糖和游离脂肪酸会损害β细胞功能，导致胰岛素分泌缺陷，最终导致β细胞衰竭。我们使用适用于INS-1Eβ细胞的半高通量方法，测试了长期暴露于基础，中等和高葡萄糖的多种情况，并结合了饱和脂肪酸与单不饱和脂肪酸和多不饱和脂肪酸，以评估细胞完整性，脂质代谢，线粒体功能，葡萄糖刺激的钙升高和分泌动力学。INS-1E beta细胞在不同的葡萄糖浓度（5.5、11.1、25 mM）下培养3天，无或有BSA复合的0.4 mM饱和（C16：0棕榈酸酯），单不饱和（C18：1油酸酯）或多不饱和（C18） ：2亚油酸酯，C18：3亚油酸酯）脂肪酸，产生0.1-0.5μM的未结合脂肪酸。暴露于脂肪酸的细胞中甘油三酸酯的积累是葡萄糖依赖性的，油酸酯可诱导最强的脂质储存并防止葡萄糖诱导的细胞毒性。长期暴露于高葡萄糖和棕榈酸酯或油酸酯的综合长期暴露会改变线粒体功能以及葡萄糖诱导的钙升高。由于棕榈酸酯和油酸酯对葡萄糖刺激的胞吐作用的第一和第二阶段表现出不同的作用，因此该模式在分泌水平上不直接翻译。两种脂肪酸都改变了激酶的活性，例如与MODY相关的BLK。另外，与棕榈酸酯相比，长期暴露于脂肪酸可通过增加膜流动性来改变膜的理化性质，油酸酯表现出更大的作用。慢性脂肪酸差异性地且特异性地加剧了某些糖毒作用，而没有自身促进细胞毒作用。每个测试的脂肪酸功能性地修饰了INS-1Eβ细胞，油酸酯诱导最强的作用。
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