OBJECTIVE Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycemia, can challenge metabolic flexibility and antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting in T2D. RESEARCH DESIGN AND METHODS Glucose-tolerant individuals (CON, n = 10), T2D individuals with (T2D+, n = 10) and without diabetes complications (T2D−, n = 10) underwent oral glucose tolerance test before and after a 5-day fasting-mimicking diet. Peripheral blood mononuclear cells’ (PBMC) resistance to ex vivo dicarbonyl methylglyoxal (MG) exposure after glucose load was assessed. Markers of dicarbonyl detoxification, oxidative stress, and mitochondrial biogenesis were analyzed by quantitative PCR, with mitochondrial complex protein expression assessed by western blotting. RESULTS T2D+ exhibited decreased PBMC resistance against MG, while T2D− resistance remained unchanged, and CON improved postglucose load and fasting (−19.0% vs.−1.7% vs. 12.6%; all P = 0.017). T2D+ showed increased expression in dicarbonyl detoxification (mRNA glyoxalase-1, all P = 0.039), oxidative stress (mRNA glutathione-disulfide-reductase, all P = 0.006), and mitochondrial complex V protein (all P = 0.004) compared with T2D− and CON postglucose load and fasting. Citrate synthase activity remained unchanged, indicating no change in mitochondrial number. Mitochondrial biogenesis increased in T2D− compared with CON postglucose load and fasting (mRNA HspA9, P = 0.032). T2D−, compared with CON, exhibited increased oxidative stress postfasting, but not postglucose load, with increased mRNA expression in antioxidant defenses (mRNA forkhead box O4, P = 0.036, and glutathione-peroxidase-2, P = 0.034), and compared with T2D+ (glutathione-peroxidase-2, P = 0.04). CONCLUSIONS These findings suggest increased susceptibility to glucose-induced oxidative stress in individuals with diabetes complications after prolonged fasting and might help in diet interventions for diabetes management.

中文翻译：

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长期禁食后的血糖负荷会增加糖尿病并发症患者的氧化应激相关反应


目的 2 型糖尿病 (T2D) 的长期分解代谢状态会因底物通量过多和高血糖而加剧，从而挑战代谢灵活性和抗氧化能力。我们研究了 T2D 长期禁食后细胞对葡萄糖负荷的反应。研究设计和方法 耐糖个体（CON，n = 10）、有糖尿病并发症的 T2D 个体（T2D+，n = 10）和无糖尿病并发症的个体（T2D−，n = 10）在 5 天之前和之后接受了口服葡萄糖耐量测试模仿禁食的饮食。评估了葡萄糖负荷后外周血单核细胞（PBMC）对离体二羰基甲基乙二醛（MG）暴露的抵抗力。通过定量 PCR 分析二羰基解毒、氧化应激和线粒体生物发生的标志物，并通过蛋白质印迹评估线粒体复合蛋白表达。结果 T2D+ 表现出 PBMC 对 MG 的抵抗力降低，而 T2D− 抵抗力保持不变，CON 改善了血糖负荷和禁食后的情况（−19.0% vs.−1.7% vs. 12.6%；所有 P = 0.017）。与 T2D− 相比，T2D+ 显示二羰基解毒（mRNA 乙二醛酶-1，所有 P = 0.039）、氧化应激（mRNA 谷胱甘肽-二硫化物还原酶，所有 P = 0.006）和线粒体复合物 V 蛋白（所有 P = 0.004）表达增加和 CON 血糖负荷后和禁食。柠檬酸合酶活性保持不变，表明线粒体数量没有变化。与葡萄糖负荷后和禁食后的 CON 相比，T2D− 中的线粒体生物合成有所增加（mRNA HspA9，P = 0.032）。与 CON 相比，T2D− 表现出禁食后氧化应激增加，但葡萄糖负荷后没有增加，抗氧化防御 mRNA 表达增加（mRNA 叉头框 O4，P = 0.036，谷胱甘肽过氧化物酶-2，P = 0。034），并与 T2D+（谷胱甘肽过氧化物酶-2，P = 0.04）进行比较。结论 这些发现表明，长期禁食后患有糖尿病并发症的个体对葡萄糖诱导的氧化应激的敏感性增加，可能有助于糖尿病管理的饮食干预。