Chronic effects of fatty acids on pancreatic β-cell function -: New insights from functional genomics
Chronic effects of fatty acids on pancreatic β-cell function -: New insights from functional genomics
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DOI：
10.2337/diabetes.53.2007.s159
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发表时间：
2004-02-01
期刊：
影响因子：
7.7
通讯作者：
Busch, AK
中科院分区：
文献类型：
--
作者：
Biden, TJ;Robinson, D;Busch, AK
2型糖尿病可被视为胰腺β细胞通过增强胰岛素分泌来补偿外周胰岛素抵抗的失败。这种失败可以解释为β细胞质量的相对损失以及分泌缺陷，包括基础分泌增强和对葡萄糖敏感性的选择性丧失。这些特征通过β细胞长期暴露于脂肪酸（FAs）而重现，这表明高脂血症可能导致代偿失调。使用油酸盐或棕榈酸盐预处理48小时的MIN6细胞，我们先前通过转录谱定义了全局基因表达的改变，并描述了已经建立的其他分泌变化（Busch A-K, Cordery D, Denyer G, Biden TJ: Diabetes, 51:977-987, 2002）。与葡萄糖刺激的胰岛素分泌适度脱钩相反，FA预处理显着增强了对急性FAs后续攻击的分泌反应。我们认为，这种从葡萄糖到FAs敏感性的明显转变可能是体内对高脂血症的适当反应，因此在β细胞对胰岛素抵抗的补偿中起积极作用。数十种基因表达的改变可能导致这种转换，而这些基因中的任何一种等位基因的变异都可能（在不同程度上）损害β细胞的代偿，从而导致从葡萄糖耐量受损到糖尿病的各种疾病。
Type 2 diabetes can be viewed as a failure of the pancreatic beta-cell to compensate for peripheral insulin resistance with enhanced insulin secretion. This failure is explained by both a relative loss of beta-cell mass as well as secretory defects that include enhanced basal secretion and a selective loss of sensitivity to glucose. These features are reproduced by chronic exposure of beta-cells to fatty acids (FAs), suggesting that hyperlipidemia might contribute to decompensation. Using MIN6 cells pretreated for 48 h with oleate or palmitate, we have previously defined alterations in global gene expression by transcript profiling and described additional secretory changes to those already established (Busch A-K, Cordery D, Denyer G, Biden TJ: Diabetes 51:977-987, 2002). In contrast to a modest decoupling of glucose-stimulated insulin secretion, FA pretreatment markedly enhanced the secretory response to an acute subsequent challenge with FAs. We propose that this apparent switch in sensitivity from glucose to FAs would be an appropriate response to hyperlipidemia in vivo and thus plays a positive role in beta-cell compensation for insulin resistance. Altered expression of dozens of genes could contribute to this switch, and allelic variations in any of these genes could (to varying degrees) impair beta-cell compensation and thus contribute to conditions ranging from impaired glucose tolerance to frank diabetes.