State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
School of Chemistry and Food Engineering, Changsha University of Science & Technology, Changsha 410114, China.
J Agric Food Chem. 2021 Jan 20;69(2):783-793. doi: 10.1021/acs.jafc.0c06445. Epub 2021 Jan 5.
The current study investigated the effects of exogenous free -(carboxymethyl) lysine (CML) from daily diet on diabetic-model Goto-Kakizaki rats. Rats were fed with free CML (2 mg/kg body weight) for 8 weeks, then metabolomics evaluation was performed on serum and urine, and biochemical and histopathologic examinations were conducted to verify metabolic results. Diabetic rats fed with free CML showed significantly increased ( < 0.05) fasting blood glucose (11.1 ± 1.07 mmol/L) and homeostasis model assessment values (homeostatic model assessment of insulin resistance: 16.0 ± 4.24; homeostatic model assessment of beta cell function: 6.66 ± 2.01; and modified beta cell function index: 11.5 ± 2.66) and a significantly altered ( < 0.05) oxidative stress level when compared to the control group. Serum and urine metabolomics showed a significantly altered ( < 0.05) level of aminomalonic acid, 2-oxoadipic acid, l-malic acid, β-alanine, 2-oxoglutaric acid, d-threitol, -acetyl-leucine, methylmalonic acid, l-cysteine, thymine, glycine, l-alanine, 4-hydroxyproline, hexadecane, succinic acid, l-ornithine, gluconolactone, maleic acid, l-lactate, tryptophan, 5-methoxyindoleacetate, γ-aminobutyric acid, homoserine, maltose, and quinolinic acid. Our results indicated that these metabolites altered by exposure to exogenous free CML were mapped to the citric acid cycle and amino acid and carbohydrate metabolism, which might be related to increased progression of diabetes and some other diabetic complications, including diabetic brain and neurological diseases, retinopathy, nephropathy, and impaired wound healing.
本研究旨在探讨外源性游离羧甲基赖氨酸（CML）对糖尿病模型 Goto-Kakizaki 大鼠的影响。大鼠自由摄入游离 CML（2mg/kg 体重）8 周后，对血清和尿液进行代谢组学评价，并进行生化和组织病理学检查以验证代谢结果。与对照组相比，摄入游离 CML 的糖尿病大鼠空腹血糖（11.1±1.07mmol/L）和稳态模型评估值（胰岛素抵抗稳态模型评估：16.0±4.24；β细胞功能稳态模型评估：6.66±2.01；改良β细胞功能指数：11.5±2.66）显著增加（<0.05），氧化应激水平也显著改变（<0.05）。血清和尿液代谢组学显示，丙氨酸、2-氧代戊二酸、苏氨酸、缬氨酸、谷氨酸、肌醇、-乙酰亮氨酸、甲基丙二酸、半胱氨酸、胸腺嘧啶、甘氨酸、丙氨酸、4-羟基脯氨酸、十六烷、琥珀酸、鸟氨酸、葡萄糖酸内酯、马来酸、L-乳酸、色氨酸、5-甲氧基色氨酸、γ-氨基丁酸、高丝氨酸、麦芽糖和喹啉酸等代谢物的水平显著改变（<0.05）。我们的结果表明，这些受外源性游离 CML 暴露影响的代谢物与柠檬酸循环以及氨基酸和碳水化合物代谢有关，这可能与糖尿病的进展和一些其他糖尿病并发症有关，包括糖尿病脑和神经疾病、视网膜病变、肾病和伤口愈合受损。
