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

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.

Oxidative modification of proteins and antioxidant status in blood of the rats with experimental acute generalized peritonitis against the background of streptozotocin-induced diabetes

“…The severe course and high mortality rates in acute inflammation of the peritoneum is often associated with concomitant pathology, among which from 7.5% to 14.0% is diabetes mellitus (Raeeszadeh et al, 2017;Ross et al, 2018;Churpii et al, 2019;Bashchenko et al, 2020;Grotelüschen et al, 2020). In the condition of chronic hyperglycemia, which emerges during diabetes mellitus, accumulation of end products of glycosylation and hypoxia intensify the generation of reactive oxygen species, which in turn are a reason of deficiencies of glutathione and superoxide dismutase and development of oxidative stress (Nesterov et al, 2018). Intensity of oxidative stress, as one of the links of pathogenesis of acute generalized peritonitis, derives from high phagocyte activity of neutrophile blood granulocytes, increase in the level of sponta-neous and induced synthesis of secondary reactive oxygen species (Savchenko et al, 2017) and is more pronounced in case of combined pathology (Verveha, 2021) as a manifestation of the syndrome of mutual aggravation.…”

“…(Ross et al, 2018;Grotelüschen et al, 2020). It has to be noted that lipids are one of the main targets of oxidation damage to reactive oxygen species, because there occurs dysbalance between formation and neutralizations of free-radical compounds (Nesterov et al, 2018). Intensification of free-radical oxidation of lipids leads to progression of the pathological processes, accompanied by lesions of the liver, first of all, as a result of damage to hepatocytes, their edema, ruination of mitochondria and lysosomes, influx of highly toxic products of cellular metabolism into blood and lysosome enzymes (Savchenko et al, 2017;Dalbaşı et al, 2020;Verveha, 2021).…”