People with diabetes mellitus have shorter telomeres compared with non-diabetic subjects. The aim of this study was to investigate an in-vitro model of telomere shortening under diabetes metabolic conditions. The mechanisms of the accelerated telomere length attrition and the potential telomere protective action of fenofibrate with related cellular mechanisms were also examined. Human dermal fibroblasts were passaged and cultured in normal (5.5 mM) or high (25 mM) D-glucose, across 7 days with hydrogen peroxide (H₂O₂), glucosamine (GA), or glycated albumin (AGEs-BSA). Relative telomere length (RTL) was determined by qPCR. The expression of shelterin complex members which regulate telomere stability were measured by qRT-PCR and Western immunoblot. Culture in high glucose decreased RTL compared with normal glucose: H₂O₂ and GA lowered the RTL after 7 days (each P < 0.05 vs untreated control), whereas AGEs-BSA had no effect compared with control-BSA. At day 7 the mRNA levels of most shelterin complex members, were induced by H₂O₂ and to a lesser extent by GA. Trf1 and Trf2 protein were induced by H₂O_2. Co-treatment with fenofibrate (100 μM) significantly attenuated the reduction in RTL caused by H₂O₂ and GA and prevented Trf induction by H₂O₂. However knockdown of Trf1 and Trf2 expression using specific siRNA did not prevent H₂O₂ effects to lower RTL, thus implicating factors other than these Trfs alone in the fenofibrate protection against the H₂O₂ induction of RTL lowering. These in vitro findings demonstrate that diabetic conditions can induce telomere shortening and that fenofibrate has protective effects on telomere attrition, through as yet undefined mechanisms.

中文翻译：

---

糖尿病中代谢因素缩短端粒长度：非诺贝特的保护作用。

与非糖尿病患者相比，糖尿病患者的端粒较短。本研究的目的是研究糖尿病代谢条件下端粒缩短的体外模型。还研究了加速端粒长度磨损的机制和非诺贝特的潜在端粒保护作用以及相关的细胞机制。人真皮成纤维细胞在正常 (5.5 mM) 或高 (25 mM) D-葡萄糖中用过氧化氢 (H ₂ O _{2 ) 传代和培养 7 天})、氨基葡萄糖 (GA) 或糖化白蛋白 (AGEs-BSA)。相对端粒长度 (RTL) 由 qPCR 确定。通过qRT-PCR和Western免疫印迹测量调节端粒稳定性的shelterin复合物成员的表达。与正常葡萄糖相比，高糖培养降低了 RTL：H ₂ O ₂和 GA 在 7 天后降低了 RTL（与未处理的对照相比，每个P  < 0.05），而 AGEs-BSA 与对照-BSA 相比没有影响。在第 7 天，大多数shelterin 复合体成员的mRNA 水平由H ₂ O ₂诱导，在较小程度上由GA 诱导。Trf1 和 Trf2 蛋白由 H ₂ O _{2 诱导。}与非诺贝特 (100 μM) 共同处理显着减弱了由 H ₂ O _{2和 GA 引起的 RTL 降低，并阻止了 H 2} O ₂对 Trf 的诱导。然而，使用特异性 siRNA 敲低Trf1和Trf2表达并不能阻止 H ₂ O ₂对降低 RTL 的影响，因此表明除了这些 Trfs 之外的因素在非诺贝特对 H ₂ O ₂诱导 RTL 降低的保护作用中。这些体外研究结果表明，糖尿病状况可诱导端粒缩短，并且非诺贝特通过尚未确定的机制对端粒磨损具有保护作用。