Abstract
l-Cysteine (LC) is an essential precursor of GSH biosynthesis. GSH is a major physiological antioxidant, and its depletion increases oxidative stress. Diabetes is associated with lower blood levels of lc and GSH. The mechanisms leading to a decrease in lc in diabetes are not entirely known. This study reports a significant decrease in LC in human monocytes exposed to high glucose (HG) concentrations as well as in the blood of type 2 diabetic rats. Thus, a significant decrease in the level of LC in response to exposure to HG supports the assertion that uncontrolled hyperglycemia contributes to a reduction of blood levels of lc and GSH seen in diabetic patients. Increased requirement of LC to replace GSH needed to scavenge excess ROS generated by hyperglycemia can result in lower levels of LC and GSH. Animal and human studies report that LC supplementation improves GSH biosynthesis and is beneficial in lowering oxidative stress and insulin resistance. This suggests that hyperglycemia has a direct role in the impairment of lc and GSH homeostasis in diabetes.
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The authors are supported by grants from NCCAM of the NIH (Grant No. RO1 AT007442), the Malcolm Feist Endowed Chair in Diabetes, and by a fellowship from the Malcolm Feist Cardiovascular Research Endowment from LSUHSC, Shreveport. The authors thank Georgia Morgan for excellent editing of this manuscript. The authors have declared that no conflict of interest exists.
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Kanikarla-Marie, P., Micinski, D. & Jain, S.K. Hyperglycemia (high-glucose) decreases l-cysteine and glutathione levels in cultured monocytes and blood of Zucker diabetic rats. Mol Cell Biochem 459, 151–156 (2019). https://doi.org/10.1007/s11010-019-03558-z
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DOI: https://doi.org/10.1007/s11010-019-03558-z