Tsuchimochi Wakaba, Ueno Hiroaki, Yamashita Eiichiro, Tsubouchi Chikako, Sakoda Hideyuki, Nakamura Shuji, Nakazato Masamitsu
Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
Endocr J. 2015;62(1):13-20. doi: 10.1507/endocrj.EJ14-0393. Epub 2014 Sep 25.
Teneligliptin is a novel peptidomimetic-chemotype prolylthiazolidine-based inhibitor of dipeptidyl peptidase-4 (DPP-4). The aim of this study was to evaluate the effects of teneligliptin on 24 h blood glucose control and gastrointestinal hormone responses to a meal tolerance test, and to investigate the glucose-lowering mechanisms of teneligliptin. Ten patients with type 2 diabetes mellitus (T2DM) were treated for 3 days with teneligliptin (20 mg/day). Postprandial profiles for glucose, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), active glucose-dependent insulinotropic polypeptide (GIP), ghrelin, des-acyl ghrelin, and 24 h glycemic fluctuations were measured via continuous glucose monitoring for 4 days. Once daily teneligliptin administration for 3 days significantly lowered postprandial and fasting glucose levels. Significant elevations of fasting and postprandial active GLP-1 and postprandial active GIP levels were observed. Teneligliptin lowered postprandial glucose elevations, 24 h mean blood glucose levels, standard deviation of 24 h glucose levels and mean amplitude of glycemic excursions (MAGE) without hypoglycemia. Serum insulin levels in the fasting state and 30 min after a meal were similar before and after teneligliptin treatment; however significant reductions at 60 to 180 min after treatment were observed. A significant elevation in early-phase insulin secretion estimated by insulinogenic and oral disposition indices, and a significant reduction in postprandial glucagon AUC were observed. Both plasma ghrelin and des-acyl ghrelin levels were unaltered following teneligliptin treatment. Teneligliptin improved 24 h blood glucose levels by increasing active incretin levels and early-phase insulin secretion, reducing the postprandial insulin requirement, and reducing glucagon secretion. Even short-term teneligliptin treatment may offer benefits for patients with T2DM.
替奈利肽是一种新型的基于脯氨噻唑烷化学结构的拟肽类二肽基肽酶-4（DPP-4）抑制剂。本研究旨在评估替奈利肽对24小时血糖控制的影响以及对进餐耐量试验的胃肠激素反应，并探究替奈利肽的降糖机制。10例2型糖尿病（T2DM）患者接受替奈利肽（20毫克/天）治疗3天。通过连续血糖监测4天来测量葡萄糖、胰岛素、胰高血糖素、活性胰高血糖素样肽-1（GLP-1）、活性葡萄糖依赖性促胰岛素多肽（GIP）、胃饥饿素、去酰基胃饥饿素的餐后曲线以及24小时血糖波动情况。连续3天每日一次给予替奈利肽可显著降低餐后和空腹血糖水平。观察到空腹和餐后活性GLP-1以及餐后活性GIP水平显著升高。替奈利肽降低了餐后血糖升高幅度、24小时平均血糖水平、24小时血糖水平标准差以及血糖波动平均幅度（MAGE），且未发生低血糖。替奈利肽治疗前后空腹状态及餐后30分钟时的血清胰岛素水平相似；然而，治疗后60至180分钟时观察到显著降低。观察到通过胰岛素生成指数和口服处置指数估计的早期胰岛素分泌显著升高，且餐后胰高血糖素曲线下面积显著降低。替奈利肽治疗后血浆胃饥饿素和去酰基胃饥饿素水平均未改变。替奈利肽通过提高活性肠促胰岛素水平和早期胰岛素分泌、减少餐后胰岛素需求以及减少胰高血糖素分泌来改善24小时血糖水平。即使短期使用替奈利肽治疗也可能对T2DM患者有益。
