Imeglimin is a new anti-diabetic drug which promotes insulin secretion from pancreatic β-cells and reduces insulin resistance in insulin target tissues. However, there have been no reports examining the possible anti-atherosclerotic effects of imeglimin. In this study, we investigated the possible anti-atherosclerotic effects of imeglimin using atherosclerosis model ApoE KO mice treated with streptozotocin (STZ). ApoE KO mice were divided into three groups: the first group was a normoglycemic group without injecting STZ (non-DM group, n = 10). In the second group, mice were injected with STZ and treated with 0.5% carboxymethyl cellulose (CMC) (control group, n = 12). In the third group, mice were injected with STZ and treated with imeglimin (200 mg/kg, twice daily oral gavage, n = 12). We observed the mice in the three groups from 10 to 18 weeks of age. Plaque formation in aortic arch and expression levels of various vascular factors in abdominal aorta were evaluated for each group. Imeglimin showed favorable effects on the development of plaque formation in the aortic arch in STZ-induced hyperglycemic ApoE KO mice which was independent of glycemic and lipid control. Migration and proliferation of vascular smooth muscle cells and infiltration of macrophage were observed in atherosclerotic lesions in STZ-induced hyperglycemic ApoE KO mice, however, which were markedly reduced by imeglimin treatment. In addition, imeglimin reduced oxidative stress, inflammation and inflammasome in hyperglycemic ApoE KO mice. Expression levels of macrophage makers were also significantly reduced by imeglimin treatment. Imeglimin exerts favorable effects on the development of plaque formation and progression of atherosclerosis.

中文翻译：

---

imeglimin 对 STZ 治疗的 ApoE KO 小鼠动脉粥样硬化的保护作用

Imeglimin是一种新型抗糖尿病药物，可促进胰腺β细胞分泌胰岛素，降低胰岛素靶组织的胰岛素抵抗。然而，目前还没有研究伊格列明可能的抗动脉粥样硬化作用的报道。在这项研究中，我们使用链脲佐菌素 (STZ) 治疗的动脉粥样硬化 ApoE KO 小鼠模型研究了 imeglimin 可能的抗动脉粥样硬化作用。ApoE KO小鼠分为三组：第一组是未注射STZ的血糖正常组（非DM组，n = 10）。第二组小鼠注射 STZ 并用 0.5% 羧甲基纤维素 (CMC) 治疗（对照组，n = 12）。在第三组中，小鼠注射 STZ 并接受伊格列明（200 mg/kg，每天两次口服灌胃，n = 12）治疗。我们观察了三组 10 至 18 周龄的小鼠。评估各组主动脉弓斑块形成和腹主动脉各种血管因子的表达水平。在 STZ 诱导的高血糖 ApoE KO 小鼠中，Imeglimin 对主动脉弓斑块形成的发展显示出有利的作用，该作用与血糖和血脂控制无关。在 STZ 诱导的高血糖 ApoE KO 小鼠的动脉粥样硬化病变中观察到血管平滑肌细胞的迁移和增殖以及巨噬细胞的浸润，而伊格列明治疗显着减少了这些现象。此外，imeglimin 可减少高血糖 ApoE KO 小鼠的氧化应激、炎症和炎性小体。巨噬细胞生成物的表达水平也因伊格列明治疗而显着降低。Imeglimin 对斑块形成的发展和动脉粥样硬化的进展发挥有利作用。