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J Diabetes Investig. 2019 Mar 1. doi: 10.1111/jdi.13032. [Epub ahead of print]

Glycine increases glyoxalase-1 function by promoting Nrf2 translocation into the nucleus of kidney cells of streptozotocin-induced diabetic rats.

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Endocrinology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
Animal Center, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.



We have previously reported that glycine suppresses the advanced glycation end-products (AGEs) signaling pathway and mitigates subsequent oxidative stress in the kidney of diabetic rats. In the present study, we investigated whether this beneficial effect was associated with up-regulation of glyoxalase-1 (Glo1) and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2).


Both healthy rats and streptozotocin-induced diabetic rats were administrated with glycine (1% added to the drinking water) for 12 weeks. The function of Glo1, mRNA and protein expressions of Nrf2, and markers of oxidative status were measured in the kidney. The mRNA expressions of other downstream signaling molecules of Nrf2 pathway were also determined.


The mRNA and protein expressions as well as the activity of Glo1 were decreased in the kidneys of diabetic rats, accompanied by diminished GSH levels. After glycine treatment, these parameters of Glo1 function were markedly increased. Comparing with the control group, the levels of Nrf2 mRNA and protein in the total kidney lysis were both markedly elevated in the diabetic group and glycine-treated group. However, the nuclear translocation of Nrf2 was significantly increased in the glycine-treated group than in the diabetic group. In addition, the antioxidant capacity and the expressions of other downstream molecules of the Nrf2 signaling pathway were significantly increased after glycine treatment.


Our study demonstrates that glycine might enhance the function of Glo1 and restore antioxidant defense by promoting the nuclear translocation of Nrf2, thus inhibiting AGEs formation and protecting against renal oxidative stress. This article is protected by copyright. All rights reserved.


glycine; glyoxalase-1; nuclear factor erythroid 2-related factor 2

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