Department of Medicine, Changi General Hospital, Singapore, Singapore.
NanoBiotechnology Laboratory, Monash University, Melbourne, Victoria, Australia.
PLoS One. 2021 Jul 14;16(7):e0254619. doi: 10.1371/journal.pone.0254619. eCollection 2021.
Diabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans.
We compared arterial blood oxygen levels in Sprague-Dawley rats after 7 days of ad libitum ELO or tap water consumption. Mitochondrial stress testing, and flow cytometry analysis of mitochondrial mass and membrane potential, were performed on human HepG2 cells cultured in four Dulbecco's Modified Eagle Medium media, made with ELO water or regular (control) water, at normal (5.5 mM) or high (25 mM) glucose concentrations. We also randomized 150 adults with type 2 diabetes (mean age 53 years, glycated haemoglobin HbA1c 8.9% [74 mmol/mol], average duration of diabetes 12 years) to drink 1.5 litres daily of bottled ELO water or drinking water.
ELO water raised arterial oxygen tension pO2 significantly (335 ± 26 vs. 188 ± 18 mmHg, p = 0.006) compared with tap water. In cells cultured in control water, mitochondrial mass and membrane potential were both significantly lower at 25 mM glucose compared with 5.5 mM glucose; in contrast, mitochondrial mass and membrane potential did not differ significantly at normal or high glucose concentrations in cells cultured in ELO water. The high-glucose environment induced a greater mitochondrial proton leak in cells cultured in ELO water compared to cells cultured in control medium at similar glucose concentration. In type 2 diabetic adults, HbA1c decreased significantly (p = 0.002) by 0.3 ± 0.7% (4 ± 8 mmol/mol), with ELO water after 12 weeks of treatment but was unchanged with placebo.
ELO water raises arterial blood oxygen levels, appears to have a protective effect on hyperglycaemia-induced reduction in mitochondrial mass and mitochondrial dysfunction, and may be effective adjuvant therapy for type 2 diabetes.
糖尿病与组织供氧不足有关。细胞缺氧与线粒体功能障碍有关，后者会增加氧化应激和高血糖。高压氧治疗已被证明可提高胰岛素敏感性，但不适合常规使用。我们评估了富氧水（ELO 水）增加动脉血氧水平对正常或高葡萄糖环境下线粒体功能的影响，以及作为人类降血糖治疗的效果。
我们比较了自由饮用 ELO 水或自来水 7 天后 Sprague-Dawley 大鼠的动脉血氧水平。我们在四种含有 ELO 水或常规（对照）水的 Dulbecco 改良 Eagle 培养基中培养人 HepG2 细胞，在正常（5.5 mM）或高（25 mM）葡萄糖浓度下进行线粒体应激测试和线粒体质量及膜电位流式细胞术分析。我们还将 150 名 2 型糖尿病成人（平均年龄 53 岁，糖化血红蛋白 HbA1c 8.9%[74 mmol/mol]，糖尿病平均病程 12 年）随机分为两组，分别每天饮用 1.5 升瓶装 ELO 水或饮用水。
ELO 水显著提高动脉血氧分压（pO2）（335 ± 26 比 188 ± 18 mmHg，p = 0.006），与自来水相比。在对照水培养的细胞中，25 mM 葡萄糖与 5.5 mM 葡萄糖相比，线粒体质量和膜电位均显著降低；相比之下，在 ELO 水培养的细胞中，正常或高葡萄糖浓度下，线粒体质量和膜电位无显著差异。与在对照培养基中培养的细胞相比，在高葡萄糖环境下，在 ELO 水培养的细胞中诱导的线粒体质子漏更大。在 2 型糖尿病成人中，ELO 水治疗 12 周后 HbA1c 显著下降（p = 0.002）0.3 ± 0.7%（4 ± 8 mmol/mol），而安慰剂组无变化。
ELO 水可提高动脉血氧水平，似乎对高血糖诱导的线粒体质量和功能障碍减少具有保护作用，可能是 2 型糖尿病的有效辅助治疗方法。
