Wang Liang-Chen, Fang Fu-Sheng, Gong Yan-Ping, Yang Guang, Li Chun-Lin
Department of Geriatric Endocrinology, Chinese PLA General Hospital National Clinical Research Center for Geriatic Diseases Department of Endocrinology, Air Force General Hospital, PLA, Beijing, China.
Medicine (Baltimore). 2018 Sep;97(38):e12476. doi: 10.1097/MD.0000000000012476.
This study aims to compare the effect of repaglinide and metformin among Chinese patients with newly diagnosed diabetes, and explore the possible mechanisms by which repaglinide alters insulin secretion.Sixty subjects with glycated hemoglobin (HbA1c) < 10.0% were randomly selected to receive repaglinide or metformin monotherapy for 15 weeks. Blood glucose levels, glycemic variability, β-cell function, and first-phase insulin secretion were compared between these 2 groups at baseline and at 15 weeks. Mouse insulinoma (MIN-6) cells were divided into 3 groups: low glucose, high glucose, and repaglinide 50 nm groups. Cells and cell culture mediums were collected at different timepoints. The expression of pericentrin (PCNT), F-actin, and insulin were tested with immunofluorescence and enzyme-linked immunosorbent assay.All glycemic parameters and variability indexes significantly decreased from baseline to 15 weeks, while no significant difference was found between these 2 groups at baseline or at 15 weeks. Furthermore, there was no significant difference found in fasting insulin and postprandial insulin at baseline and at 15 weeks, while homeostasis model assessment β significantly increased. The first-phase glucose and insulin secretion of the intravenous glucose tolerance test improved in both groups, especially in the repaglinide group. Insulin, PCNT, and F-actin expression in MIN-6 cells decreased after 15 minutes of stimulation with repaglinide, while no difference was observed at 2, 6, and 12 hours. The insulin levels of the cell medium in the repaglinide group remained significantly higher at all timepoints.This study manifests that repaglinide has a noninferiority effect on the glycemic parameters of Chinese patients with newly diagnosed diabetes, when compared with metformin. The PCNT-F-actin pathway plays an important role in the repaglinide regulation process of on-demand insulin secretion.
本研究旨在比较瑞格列奈与二甲双胍对中国新诊断糖尿病患者的疗效，并探讨瑞格列奈改变胰岛素分泌的可能机制。选取60例糖化血红蛋白（HbA1c）<10.0%的受试者，随机接受瑞格列奈或二甲双胍单药治疗15周。比较两组在基线和15周时的血糖水平、血糖变异性、β细胞功能和第一相胰岛素分泌。将小鼠胰岛素瘤（MIN-6）细胞分为3组：低糖组、高糖组和瑞格列奈50 nM组。在不同时间点收集细胞和细胞培养基。采用免疫荧光和酶联免疫吸附测定法检测中心粒蛋白（PCNT）、F-肌动蛋白和胰岛素的表达。所有血糖参数和变异性指标从基线到15周均显著降低，而两组在基线或15周时无显著差异。此外，基线和15周时空腹胰岛素和餐后胰岛素无显著差异，而稳态模型评估β显著升高。两组静脉葡萄糖耐量试验的第一相葡萄糖和胰岛素分泌均有改善，尤其是瑞格列奈组。瑞格列奈刺激15分钟后，MIN-6细胞中胰岛素、PCNT和F-肌动蛋白表达降低，而在2、6和12小时未观察到差异。瑞格列奈组细胞培养基中的胰岛素水平在所有时间点均显著更高。本研究表明，与二甲双胍相比，瑞格列奈对中国新诊断糖尿病患者的血糖参数具有非劣效性作用。PCNT-F-肌动蛋白途径在瑞格列奈按需调节胰岛素分泌过程中起重要作用。
