Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 69, Issue 2, Pages 783-793Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.0c06445
Keywords
serum and urine metabolomics; N-epsilon-carboxymethyllysine; advanced glycation end-products; diabetes; diabetic complications
Funding
- National Key R&D Program of China [2017YFC1600405]
- Key Research and Development Plan of Guangdong Province, China [2019B020212011]
- National First-class Discipline Program of Food Science and Technology [JUFSTR20180201]
- Innovation and Exploration Fund of State Key Laboratory of Food Science and Technology, Jiangnan University [SKLF-ZZA-202001]
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This study investigated the impact of exogenous free N-epsilon-(carboxymethyl) lysine (CML) from daily diet on diabetic-model Goto-Kakizaki rats. The results showed that feeding diabetic rats with free CML led to increased blood glucose levels and altered oxidative stress, as well as significant changes in various metabolites related to citric acid cycle and amino acid and carbohydrate metabolism, potentially contributing to the progression of diabetes and its complications.
The current study investigated the effects of exogenous free N-epsilon-(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 (P < 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 (P < 0.05) oxidative stress level when compared to the control group. Serum and urine metabolomics showed a significantly altered (P < 0.05) level of aminomalonic acid, 2-oxoadipic acid, L-malic acid, beta-alanine, 2-oxoglutaric acid, D-threitol, N-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, gamma-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.
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