Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells.
Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells.
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DOI：
10.1186/1476-511x-10-115
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发表时间：
2011-07-11
影响因子：
4.5
通讯作者：
Bergsten P
中科院分区：
文献类型：
--
作者：
Sargsyan E;Bergsten P
脂质水平长期升高对β细胞功能和质量有负面影响（脂毒性）。在何种程度上暴露于高葡萄糖浓度对脂质有害影响（糖脂毒性）是重要的一直存在争议。我们通过测量分离的完整对照人胰岛和胰岛素分泌细胞系MIN6和INS-1E在棕榈酸盐和低（5.5 mM）或高（25 mM）葡萄糖存在下培养48小时的凋亡来研究β细胞脂肪毒性。在低糖培养后，棕榈酸盐诱导细胞系和胰岛细胞凋亡。与低糖培养相比，棕榈酸盐诱导的人胰岛细胞和MIN6细胞的凋亡在高糖培养后没有增加，但在INS-1E细胞中观察到葡萄糖诱导的凋亡增加。ampk激动剂AICAR的加入部分逆转了INS-1E细胞凋亡的增加。当在低糖培养过程中加入cpt1抑制剂依托莫西时，胰岛和细胞系的棕榈酸触发的细胞凋亡都加剧了。在低糖培养后，棕榈酸在人胰岛和细胞系中的氧化是相似的。在高糖条件下，人胰岛和MIN6细胞的棕榈酸氧化降低了30%，而INS-1E细胞的棕榈酸氧化降低了80%。在INS-1E细胞中，AICAR增加棕榈酸盐的氧化。在低糖条件下使用依托莫西可降低胰岛和细胞系中棕榈酸酯的氧化。总之，脂肪毒性不仅在葡萄糖浓度高的情况下很明显，而且在葡萄糖浓度低的情况下也很明显。葡萄糖的其他作用在INS-1E中很突出，但在MIN6细胞和完整对照的人类胰岛中则不明显，后者能够在高葡萄糖条件下有效氧化脂肪酸，从而避免糖脂毒性。
Prolonged elevated levels of lipids have negative effects on beta-cell function and mass (lipotoxicity). To what extent exposure to high glucose concentration is important in the harmful effects of lipids (glucolipotoxicity) has been debated. We addressed beta-cell lipotoxicity by measuring apoptosis in isolated intact control human islets and insulin-secreting cell lines MIN6 and INS-1E cultured in the presence of palmitate and low (5.5 mM) or high (25 mM) glucose for 48 hours. In both cell lines and human islets palmitate induced apoptosis after culture at low glucose. Palmitate-induced apoptosis was not increased after culture at high compared to low glucose in human islets and MIN6 cells but glucose-induced rise in apoptosis was observed in INS-1E cells. The rise in apoptosis in INS-1E cells was partially reversed by inclusion of AMPK-agonist AICAR. When CPT1-inhibitor etomoxir was included during culture at low glucose palmitate-triggered apoptosis was accentuated both in the islets and the cell lines. Palmitate oxidation in human islets and the cell lines was comparable after culture at low glucose. At high glucose, palmitate oxidation was reduced by 30% in human islets and MIN6 cells but by 80% in INS-1E cells. In INS-1E cells, AICAR increased oxidation of palmitate. Presence of etomoxir at low glucose decreased palmitate oxidation both in the islets and the cell lines. In summary, lipotoxicity is evident not only in the presence of high but also low glucose concentrations. Additional effects of glucose are prominent in INS-1E but not in MIN6 cells and intact control human islets, which are able to efficiently oxidize fatty acids at high glucose and in this way avoid glucolipotoxicity.