Taurine supplementation restored the changes in pancreatic islet mitochondria in the fetal protein-malnourished rat
Taurine supplementation restored the changes in pancreatic islet mitochondria in the fetal protein-malnourished rat
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DOI：
10.1017/s0007114511001632
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发表时间：
2011-10-01
影响因子：
3.6
通讯作者：
Lee, Hong Kyu
中科院分区：
文献类型：
--
作者：
Lee, Yun Yong;Lee, Hwa-Jung;Lee, Hong Kyu
子宫内发育迟缓与以后患2型糖尿病有关。线粒体变化被认为是胎儿营养不良和成人胰岛素抵抗之间的联系。牛磺酸参与了这个过程。我们研究了早期蛋白质营养不良是否会改变成年后胰岛的线粒体，以及补充牛磺酸是否能恢复这些变化。在怀孕和哺乳期分别饲喂对照饮食、低蛋白饮食或添加牛磺酸的低蛋白饮食的雄性后代断奶后开始饲喂对照饮食。在每组小鼠20周龄时，进行静脉葡萄糖耐量试验、血糖-高胰岛素钳夹研究、胰岛形态计量学分析和β细胞线粒体超微结构分析。测定细胞色素c氧化酶（COX） I和线粒体呼吸链复合体II的表达。胎儿蛋白质营养不良的大鼠表现出胰岛质量下降和对葡萄糖负荷的胰岛素分泌反应降低。这些大鼠在胰岛中也表现出线粒体dna编码的COX I基因表达减少。电镜检查显示胎儿蛋白质营养不良大鼠β细胞线粒体形状异常。在低蛋白饮食中补充牛磺酸可以恢复所有这些变化。我们的研究结果表明，母亲的蛋白质限制饮食会导致长期的线粒体变化，这可能会导致以后患2型糖尿病。牛磺酸的缺乏可能是导致这些线粒体功能失调变化的关键因素。
Intra-uterine growth retardation has been linked to the development of type 2 diabetes in later life. Mitochondrial changes have been suggested as a link between fetal malnutrition and adult insulin resistance. Taurine has been implicated in this process. We investigated whether protein malnutrition in early life alters mitochondria of the pancreatic islets in adulthood, and whether taurine supplementation restores these changes. Male offspring of rats fed a control diet, a low-protein diet or a low-protein diet supplemented with taurine during pregnancy and lactation were weaned onto the control diet. In each group, at 20 weeks of age, intravenous glucose tolerance tests, euglycaemic-hyperinsulinaemic clamp studies, morphometric analysis of the pancreatic islets and ultra-structural analysis of the mitochondria of the beta-cells were performed. The expressions of cytochrome c oxidase (COX) I and mitochondrial respiratory chain complex II were also measured. Fetal protein-malnourished rats showed decreased pancreatic islet mass and reduced insulin-secretory responses to a glucose load. These rats also showed reduced mitochondrial DNA-encoded COX I gene expression in the islets. Electron microscopic examination showed abnormal mitochondrial shapes in the beta-cells of fetal protein-malnourished rats. Taurine supplementation to the low-protein diet restored all these changes. Our findings indicate that a maternal protein-restriction diet causes long-lasting mitochondrial changes that may contribute to the development of type 2 diabetes later in life. The lack of taurine may be a key causative factor for these dysfunctional mitochondrial changes.