Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
PLoS One. 2020 Feb 7;15(2):e0228750. doi: 10.1371/journal.pone.0228750. eCollection 2020.
Accumulating epidemiological studies have demonstrated that diabetes is an important risk factor for dementia. However, the underlying pathological and molecular mechanisms, and effective treatment, have not been fully elucidated. Herein, we investigated the effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, on diabetes-related cognitive impairment.
Streptozotocin (STZ)-induced diabetic mice were treated with linagliptin (3 mg/kg/24 h) for 17 weeks. The radial arm water maze test was performed, followed by evaluation of oxidative stress using DNP-MRI and the expression of NAD(P)H oxidase components and proinflammatory cytokines and of microglial activity.
Administration of linagliptin did not affect the plasma glucose and body weight of diabetic mice; however, it improved cognitive impairment. Additionally, linagliptin reduced oxidative stress and the mRNA expression of NAD(P)H oxidase component and TNF-α, and the number and body area of microglia, all of which were significantly increased in diabetic mice.
Linagliptin may have a beneficial effect on diabetes-related dementia by inhibiting oxidative stress and microglial activation, independently of glucose-lowering.
越来越多的流行病学研究表明，糖尿病是痴呆的一个重要危险因素。然而，其潜在的病理和分子机制以及有效的治疗方法尚未完全阐明。在此，我们研究了二肽基肽酶-4（DPP-4）抑制剂利拉利汀对与糖尿病相关的认知障碍的影响。
用链脲佐菌素（STZ）诱导糖尿病小鼠，用利拉利汀（3 mg/kg/24 h）治疗 17 周。进行放射臂水迷宫测试，然后使用 DNP-MRI 评估氧化应激，以及 NAD（P）H 氧化酶成分和促炎细胞因子的表达和小胶质细胞的活性。
利拉利汀的给药不影响糖尿病小鼠的血浆葡萄糖和体重；然而，它改善了认知障碍。此外，利拉利汀降低了氧化应激和 NAD（P）H 氧化酶成分和 TNF-α的 mRNA 表达，以及糖尿病小鼠中小胶质细胞的数量和体区，所有这些都显著增加。
利拉利汀可能通过抑制氧化应激和小胶质细胞激活对与糖尿病相关的痴呆症有有益的影响，而不依赖于降血糖。
