Quan Yi, Luo Kang, Cui Sheng, Lim Sun Woo, Shin Yoo Jin, Ko Eun Jeong, Kim Ju Hwan, Chung Sang J, Bae Soo Kyung, Chung Byung Ha, Yang Chul Woo
Transplant Research Center, The Catholic University of Korea, Seoul, Korea.
Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea, Seoul, Korea.
Korean J Intern Med. 2020 Nov;35(6):1443-1456. doi: 10.3904/kjim.2019.269. Epub 2020 Apr 14.
BACKGROUND/AIMS: Coenzyme Q10 (CoQ10) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ10-based micelle formulation (CoQ10-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM).
We developed CoQ10-W from a glycyrrhizic-carnitine mixed layer CoQ10 micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ10 (CoQ10-L) or CoQ10-W for 4 weeks. Their plasma and pancreatic CoQ10 concentrations were measured using liquid chromatography- tandem mass spectrometry. The therapeutic efficacies of CoQ10-W and CoQ10-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells.
The plasma CoQ10 level was significantly increased in the CoQ10-W group compared to that in the CoQ10-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ10-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ10-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ10-W but not by CoQ10-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ10-W than CoQ10-L. Electron microscopy revealed that CoQ10-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ10-L. In vitro studies showed that CoQ10-L and CoQ10-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent.
CoQ10-W has better therapeutic efficacy than CoQ10-L in TAC-induced DM.
背景/目的：辅酶Q10（CoQ10）具有抗氧化作用，且已商业化并广泛销售。然而，由于其生物利用度低，其效果仍存在争议。我们开发了一种基于水溶性CoQ10的胶束制剂（CoQ10-W），并在他克莫司（TAC）诱导的糖尿病（DM）实验模型中对其进行了测试。
我们从基于酰基转移酶的甘草酸-肉碱混合层CoQ10胶束制剂中开发出CoQ10-W。将TAC诱导的DM大鼠用脂溶性CoQ10（CoQ10-L）或CoQ10-W治疗4周。使用液相色谱-串联质谱法测量它们的血浆和胰腺CoQ10浓度。使用功能和形态学参数比较CoQ10-W和CoQ10-L对TAC诱导的DM的治疗效果，并在培养的大鼠胰岛素瘤细胞中评估它们对细胞活力和活性氧（ROS）产生的影响。
与CoQ10-L组相比，CoQ10-W组的血浆CoQ10水平显著升高。腹腔内葡萄糖耐量试验和葡萄糖刺激的胰岛素分泌显示，CoQ10-W在控制高血糖和恢复胰岛素分泌方面明显优于CoQ10-L。CoQ10-W显著减轻了TAC介导的胰岛大小减小，但CoQ10-L没有。CoQ10-W比CoQ10-L更能显著降低TAC诱导的氧化应激和细胞凋亡。电子显微镜显示，与CoQ10-L不同，CoQ10-W恢复了TAC诱导的胰岛素颗粒数量和平均线粒体面积的减少。体外研究表明，CoQ10-L和CoQ10-W在改善TAC处理的胰岛细胞的细胞活力和降低ROS产生方面程度相似。
在TAC诱导的DM中，CoQ10-W比CoQ10-L具有更好的治疗效果。
