Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, Pisa University Hospital, Pisa, Italy.
Horm Metab Res. 2012 Jun;44(6):471-5. doi: 10.1055/s-0032-1301920. Epub 2012 Mar 7.
Frataxin (FXN) is a mitochondrial protein involved in iron metabolism and in the modulation of reactive oxygen and/or nitrogen species production. No information is currently available as for the role of frataxin in isolated human pancreatic islets. We studied islets from pancreases of multi-organ donors with (T2DM) and without (Ctrl) Type 2 diabetes mellitus. In these islets, we determined FXN gene and protein expression by qualitative and quantitative Real-Time RT-PCR, nitrotyrosine concentration, and insulin release in response to glucose stimulation (SI). FXN gene and protein were expressed in human islets, though the level of expression was much lower in T2DM islets. The latter also had lower insulin release and higher concentration of nitrotyrosine. A positive correlation was apparent between SI and FXN gene expression, while a negative correlation was found between nitrotyrosine islet concentration and FXN expression. Transfection of Ctrl islets with siRNA FXN caused reduction of FXN expression, increase of nitrotyrosine concentration, and reduction of insulin release. In conclusion, in human pancreatic islets FXN contributes to regulation of oxidative stress and insulin release in response to glucose. In islets from T2DM patients FXN expression is reduced while oxidative stress is increased and insulin release in response to glucose impaired.
铁蛋白（FXN）是一种参与铁代谢和调节活性氧和/或氮物种产生的线粒体蛋白。目前尚无关于铁蛋白在分离的人胰岛中的作用的信息。我们研究了来自多器官供体的胰岛，这些供体患有（T2DM）和不患有（Ctrl）2 型糖尿病。在这些胰岛中，我们通过定性和定量实时 RT-PCR、硝基酪氨酸浓度和葡萄糖刺激（SI）下的胰岛素释放来确定 FXN 基因和蛋白表达。FXN 基因和蛋白在人胰岛中表达，但在 T2DM 胰岛中表达水平低得多。后者的胰岛素释放也较低，硝基酪氨酸浓度较高。SI 与 FXN 基因表达之间存在明显的正相关，而胰岛中硝基酪氨酸浓度与 FXN 表达之间存在负相关。用 siRNA FXN 转染 Ctrl 胰岛可导致 FXN 表达减少、硝基酪氨酸浓度增加和胰岛素释放减少。总之，在人胰岛中，FXN 有助于调节氧化应激和葡萄糖刺激下的胰岛素释放。在 T2DM 患者的胰岛中，FXN 表达减少，而氧化应激增加，对葡萄糖的胰岛素释放受损。
