Imeglimin hydrochloride is an oral glucose-lowering agents, inhibiting Multidrug and toxin extrusion protein 1 (MATE1) with an IC50 value of 19.24μM[1]. Imeglimin hydrochloride has been widely used in anti-diabetes research and mitochondrial function research[2].
In vitro, Imeglimin hydrochloride (10mM; 4 hours) treatment can prevent cell death of HMEC-1 cells caused by tBH and hyperglycemia, and block the release of cytochrome c[3]. The human hepatoma cell line HepG2 was treated with Imeglimin hydrochloride at a concentration of 10mM for 3 hours, resulting in a significant decrease in the oxygen consumption rate (OCR) under the basal state, along with a significant decrease in ATP production[4]. When treated at a concentration of 1mM for 48 hours, Imeglimin hydrochloride significantly weakened the activity of mitochondrial complex I in 3T3-L1 adipocytes and promoted the synthesis and secretion of mitochondrial factors in adipocytes[5].
In vivo, Imeglimin hydrochloride treatment through oral gavage at a dose of 50mg/kg/day for 9 weeks reduced the area of atherosclerotic plaques, decreased fasting blood glucose and low-density lipoprotein cholesterol levels in diabetic ApoE-/- mice[6]. Oral administration of Imeglimin hydrochloride at a dose of 200mg/kg twice a day for 60 days can protect mitochondrial function from oxidative stress and promote lipid oxidation in the liver of high-fat and high-sugar diet (HFHSD) mouse models, restoring normal glucose tolerance and insulin sensitivity[7].
References:
[1]Clémence C, Fouqueray P, Sébastien B. In vitro investigation, pharmacokinetics, and disposition of imeglimin, a novel oral antidiabetic drug, in preclinical species and humans[J]. Drug Metabolism and Disposition, 2020, 48(12): 1330-1346.
[2]Chevalier C, Perrimond-Dauchy S, Dubourg J, et al. Lack of drug–drug interaction between cimetidine, a renal transporter inhibitor, and imeglimin, a novel oral antidiabetic drug, in healthy volunteers[J]. European Journal of Drug Metabolism and Pharmacokinetics, 2020, 45: 725-733.
[3]Detaille D, Vial G, Borel A L, et al. Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration[J]. Cell death discovery, 2016, 2(1): 1-8.
[4]Hozumi K, Sugawara K, Ishihara T, et al. Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes[J]. Scientific Reports, 2023, 13(1): 746.
[5]Takahashi N, Kimura A P, Yoshizaki T, et al. Imeglimin modulates mitochondria biology and facilitates mitokine secretion in 3T3-L1 adipocytes[J]. Life Sciences, 2024, 349: 122735.
[6]Lee J Y, Kang Y, Jeon J Y, et al. Imeglimin Inhibits Macrophage Foam Cell Formation and Atherosclerosis in Streptozotocin-Induced Diabetic ApoE-Deficient Mice[J]. Cells, 2025, 14(7): 472.
[7]Vial G, Chauvin M A, Bendridi N, et al. Imeglimin normalizes glucose tolerance and insulin sensitivity and improves mitochondrial function in liver of a high-fat, high-sucrose diet mice model[J]. Diabetes, 2015, 64(6): 2254-2264.
Imeglimin hydrochloride是一种口服降糖药物，可抑制多药及毒素外排蛋白1（MATE1），IC50值为19.24μM[1]。Imeglimin hydrochloride在抗糖尿病研究和线粒体功能研究中具有广泛应用价值[2]。
在体外，当使用10mM浓度的Imeglimin hydrochloride处理HMEC-1细胞4小时后，能够有效阻止叔丁基过氧化氢（tBH）和高糖诱导的细胞死亡，并阻断细胞色素c的释放[3]。在人肝癌细胞系HepG2中，10mM浓度的Imeglimin hydrochloride处理3小时可显著降低基础状态下的氧消耗速率（OCR），同时减少ATP生成[4]。在3T3-L1脂肪细胞中，1mM浓度的Imeglimin hydrochloride处理48小时能明显减弱线粒体复合物I的活性，并促进脂肪细胞中多种线粒体因子的合成与分泌[5]。
在体内，糖尿病ApoE-/-小鼠模型经50mg/kg/day剂量的Imeglimin hydrochloride口服灌胃治疗9周后，动脉粥样硬化斑块面积显著缩小，空腹血糖和低密度脂蛋白胆固醇水平明显降低[6]。在高脂高糖饮食（HFHSD）小鼠模型中，每日两次、每次200mg/kg剂量的Imeglimin hydrochloride连续给药60天，可保护肝脏线粒体功能免受氧化应激损伤，促进肝脏脂质氧化代谢，使葡萄糖耐量和胰岛素敏感性恢复正常水平[7]。