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.