Yako Hideji, Suzuki Mari, Takaku Shizuka, Niimi Naoko, Kato Ayako, Kato Koichi, Yamauchi Junji, Sango Kazunori
Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0982, Japan.
Int J Mol Sci. 2025 May 13;26(10):4666. doi: 10.3390/ijms26104666.
Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus for which effective treatments remain undeveloped. Metabolic changes and inflammation are proposed as primary mechanisms underlying DPN pathogenesis. Our previous studies demonstrate that exogenous pyruvate plays a crucial role in maintaining glycolysis-tricarboxylic acid cycle flux under high-glucose conditions and also exhibits anti-inflammatory properties. To evaluate its therapeutic potential, we assessed whether pyruvate administration could restore DPN in vivo and in vitro. We assessed casual blood glucose levels, body weight, motor and sensory nerve conduction velocities, mechanical sensitivity, and intraepidermal nerve fiber density in streptozotocin-induced diabetic C57/BL/6J mice that received drinking water with or without sodium pyruvate (10 mg/mL) from 2 to 13 weeks after diabetes induction. In addition, we evaluated neurite length in ND7/23 cells, a dorsal root ganglion neuron cell line, under high-glucose conditions. Pyruvate administration in diabetic mice alleviated mechanical sensitivity deficits and improved intraepidermal nerve fiber density. Additionally, neurite length in ND7/23 cells was inhibited under high-glucose conditions but was fully restored by supplementation with high concentrations (10 mM) of pyruvate. These findings suggest that exogenous pyruvate may be a promising therapeutic candidate for DPN.
糖尿病周围神经病变（DPN）是糖尿病的一种慢性并发症，目前尚未开发出有效的治疗方法。代谢变化和炎症被认为是DPN发病机制的主要原因。我们之前的研究表明，外源性丙酮酸在高糖条件下维持糖酵解-三羧酸循环通量方面起着关键作用，并且还具有抗炎特性。为了评估其治疗潜力，我们评估了给予丙酮酸是否能在体内和体外恢复DPN。我们评估了链脲佐菌素诱导的糖尿病C57/BL/6J小鼠的随机血糖水平、体重、运动和感觉神经传导速度、机械敏感性以及表皮内神经纤维密度，这些小鼠在糖尿病诱导后2至13周饮用含或不含丙酮酸钠（10 mg/mL）的水。此外，我们评估了高糖条件下背根神经节神经元细胞系ND7/23细胞的神经突长度。给糖尿病小鼠施用丙酮酸可减轻机械敏感性缺陷并改善表皮内神经纤维密度。此外，ND7/23细胞的神经突长度在高糖条件下受到抑制，但通过补充高浓度（10 mM）的丙酮酸可完全恢复。这些发现表明，外源性丙酮酸可能是DPN的一种有前景的治疗候选物。
