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Autocatalytic cycle in the pathogenesis of diabetes mellitus: biochemical and pathophysiological aspects of metabolic therapy with natural amino acids on the example of glycine

https://doi.org/10.14341/DM9529

Abstract

In this work systematization (classification) of biochemical and physiological processes that cause disorders in the human body during the development of diabetes mellitus is carried out. The development of the disease is considered as the interaction and mutual reinforcement of two groups of parallel processes. The first group has a molecular nature and it is associated with impairment of ROS-regulation system which includes NADPH oxidases, RAGE receptors, mitochondria, cellular peroxireductase system and the immune system. The second group has a pathophysiological nature and it is associated with impairment of microcirculation and liver metabolism. The analysis of diabetes biochemistry based on different published references yields a creation of a block diagram evaluating the disease development over time. Two types of autocatalytic processes were identified: autocatalysis in the cascade of biochemical reactions and "cross-section" catalysis, in which biochemical and pathophysiological processes reinforce each other. The developed model has shown the possibility of using pharmacologically active natural metabolite glycine as a medicine inhibiting the development of diabetes. Despite the fact that glycine is a substitute amino acid the drop in the glycine blood concentration occurs even in the early stages of diabetes development and can aggravate the disease. It is shown that glycine is a potential blocker of key autocatalytic cycles, including biochemical and pathophysiological processes. The analysis of the glycine action based on the developed model is in complete agreement with the results of clinical trials in which glycine has improved blood biochemistry of diabetic patients and thereby it prevents the development of diabetic complications.

About the Authors

Semen V. Nesterov

Institute of Cytochemistry and Molecular Pharmacology; Moscow Institute of Physics and Technology


Russian Federation

Junior Researcher, Department of Bioenergy; graduate student



Lev S. Yaguzhinsky

Institute of Cytochemistry and Molecular Pharmacology; A.N. Belozersky Institute of Physico-Chemical Biology MSU


Russian Federation

PhD in Biology, Professor



Gennady I. Podoprigora

Institute of Cytochemistry and Molecular Pharmacology


Russian Federation

MD, PhD, Professor



Yaroslav R. Nartsissov

Institute of Cytochemistry and Molecular Pharmacology


Russian Federation

PhD, associate professor



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Supplementary files

1. Table 1
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2. Fig. 1. Scheme of increasing the level of reactive oxygen species and the development of the inflammatory process in diabetes mellitus. The description of the numbered stages with references to the literature, as well as the description of the action of glycine at each stage are given in table 1. Autocatalytic cycles are described in detail in the main text of the article. Abbreviations: ROS — reactive oxygen species; RAGE - receptors for glycation end products; NOX - NADPH oxidase; NF-κB - Kappa-Bi nuclear factor; SOD - superoxide dismutase.
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3. Fig. 2. Scheme of the main autocatalytic cycle of mutual amplification of ROS-dependent processes and the pathophysiological process of impaired microcirculation. The degree of activity of immune cells increases due to the release of inflammatory cytokines with ROS-dependent activation of NF-κB. As a result of an autocatalytic increase in oxidative stress, there is a depletion of antioxidant protection of cells and apoptosis (or necrosis). Abbreviations: ROS — reactive oxygen species; CNG - the end products of glycation; RAGE - CNG receptors; NOX - NADPH oxidase.
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For citations:


Nesterov S.V., Yaguzhinsky L.S., Podoprigora G.I., Nartsissov Ya.R. Autocatalytic cycle in the pathogenesis of diabetes mellitus: biochemical and pathophysiological aspects of metabolic therapy with natural amino acids on the example of glycine. Diabetes mellitus. 2018;21(4):283-292. https://doi.org/10.14341/DM9529

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