Kondo Masumi, Sawada Kaichiro, Matsuda Yosuke, Abe Makiko, Sanechika Noriyuki, Takanashi Yumi, Mori Yoshitaka, Kimura Moritsugu, Toyoda Masao
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University Hachioji Hospital, 1838 Ishikawacho, Hachioji 192-0032, Japan.
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan.
Biomedicines. 2024 Aug 6;12(8):1771. doi: 10.3390/biomedicines12081771.
Deuterium-depleted water (DDW) is used in the treatment of many diseases, including cancer and diabetes. To detect the effect of DDW on gene expression and activation of the insulin-responsive transporter GLUT4 as a mechanism for improving the pathology of diabetes, we investigated the GLUT4 expression and glucose uptake at various concentrations of DDW using the myoblast cell line C2C12 differentiated into myotubes. GLUT4 gene expression significantly increased under deuterium depletion, reaching a maximum value at a deuterium concentration of approximately 50 ppm, which was approximately nine times that of natural water with a deuterium concentration of 150 ppm. GLUT4 protein also showed an increase at similar DDW concentrations. The membrane translocation of GLUT4 by insulin stimulation reached a maximum value at a deuterium concentration of approximately 50-75 ppm, which was approximately 2.2 times that in natural water. Accordingly, glucose uptake also increased by up to 2.2 times at a deuterium concentration of approximately 50 ppm. Drug-induced insulin resistance was attenuated, and the glucose uptake was four times higher in the presence of 10 ng/mL TNF-α and three times higher in the presence of 1 μg/mL resistin at a deuterium concentration of approximately 50 ppm relative to natural water. These results suggest that DDW promotes GLUT4 expression and insulin-stimulated activation in muscle cells and reduces insulin resistance, making it an effective treatment for diabetes.
低氘水（DDW）被用于治疗多种疾病，包括癌症和糖尿病。为了检测低氘水对基因表达的影响以及胰岛素反应性转运体GLUT4的激活情况，以此作为改善糖尿病病理的一种机制，我们使用分化为肌管的成肌细胞系C2C12，研究了不同浓度低氘水条件下的GLUT4表达和葡萄糖摄取。在低氘情况下，GLUT4基因表达显著增加，在氘浓度约为50 ppm时达到最大值，这大约是氘浓度为150 ppm的天然水的九倍。在相似的低氘水浓度下，GLUT4蛋白也呈现增加。胰岛素刺激引起的GLUT4膜转位在氘浓度约为50 - 75 ppm时达到最大值，这大约是天然水中的2.2倍。相应地，在氘浓度约为50 ppm时，葡萄糖摄取也增加了高达2.2倍。药物诱导的胰岛素抵抗得到减弱，相对于天然水，在氘浓度约为50 ppm时，在存在10 ng/mL肿瘤坏死因子-α（TNF-α）的情况下葡萄糖摄取高出四倍，在存在1 μg/mL抵抗素的情况下高出三倍。这些结果表明，低氘水促进肌肉细胞中GLUT4的表达和胰岛素刺激的激活，并降低胰岛素抵抗，使其成为糖尿病的一种有效治疗方法。
