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Decreased blood levels of glyoxalase I and diabetic complications

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Abstract

The formation of Advanced Glycation Endproducts (AGEs) has been found to play a role in the development of diabetic symptoms. Production of methylglyoxal (MG), a highly cytotoxic and crosslinking aldehyde, is elevated among patients with type 2 diabetes mellitus (T2DM) and is a precursor to AGEs. The ubiquitous glyoxalase system is one of several defense mechanisms involved in MG metabolism and the protection against the production of AGEs. The system is a complex of two enzymes: glyoxalase I (GloI) that converts MG and reduced glutathione (GSH) to S-lactoylglutathione which is converted to D-lactic acid by glyoxalase II, regenerating GSH in the process. The malfunctioning of the glyoxalase system results in the accumulation of MG. The present study was performed to explore the relationship between the decreased activity of GloI and the complications associated to T2DM. The activities of the GloI, GloII and the concentration of GSH were measured in blood samples of 203 volunteers: 75 controls, 60 non-insulino-dependent diabetes mellitus (NIDDM) individuals and 68 NIDDM patients with complications as follow: 18 with nephropathy, 15 with retinopathy, 15 with neuropathy and 20 with macroangiopathy. All individuals were from the northen region of Morocco. We also evaluated the relationships between GloI levels and the pathogenesis of micro- and macrovascular complications of diabetes. We found a significant decrease in the GloI activity and GSH levels in patients with diabetes compared to controls. GloI activity was further reduced in samples from diabetes patients with complications. The levels of GloI were markedly lower in blood samples from patients with nephropathy than in uncomplicated patients and normal subjects. In contrast, there was no significant change in the activity of GloII in NIDDM patients compared to controls. This study suggests that the low level of GloI activity in T2DM patients is most probably due to decreased level of GSH content and reflects the role of GloI enzyme in protecting T2DM patients from AGEs accumulation and further complications.

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Acknowledgments

We would like to thank the Regional Delegate of health and the public medical team in Tangier and Tetouan for their services and assistance in blood sampling. We would like to also thank Dr. Ahmed Lazrak (University of Alabama at Birmingham, Department of Anesthesiology) for helpful revision and Dr. Abdeloihid Elmoussaoui (FST of Tangier) for helpful statistical analysis. This study is supported by the research funds of the University of Abdelmalek Essaâdi, Tangier, Morocco.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Faculté des Sciences et Techniques de Tanger, Laboratoire de Biochimie et Génétique Moléculaire, Université Abdelmalek Essaâdi, B.P. 416, 90000, Tanger, Maroc

    Meriem Hamoudane, Amina Amakran, Naima Bakrim & Mohamed Nhiri

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  1. Meriem Hamoudane
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  2. Amina Amakran
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  3. Naima Bakrim
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  4. Mohamed Nhiri
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Correspondence to Mohamed Nhiri.

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Meriem Hamoudane and Amina Amakran are contributed equally to this work

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Hamoudane, M., Amakran, A., Bakrim, N. et al. Decreased blood levels of glyoxalase I and diabetic complications. Int J Diabetes Dev Ctries 35 (Suppl 3), 496–501 (2015). https://doi.org/10.1007/s13410-014-0237-4

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  • DOI: https://doi.org/10.1007/s13410-014-0237-4

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