Abstract

  Insulin is one of the most important of anabolic hormones. Type 2 Diabetes (T2D) is characterized by persistent, stealth catabolism, as well as impaired glucose and phosphate uptake. The phosphate transporting capability of insulin has been known for a long time, although it has been studied mainly since the 21^st century. According to the logic of the Momentary Intracellular Ion-Pattern Signaling (see Part 1.), insulin should increase of HPO₄^2- in the cytosol - and does it, indeed. (It is not clear that this is a one- or multistep membrane-transport phenomenon.) Insulin does not only stimulate the transport of phosphate (Pi) into the cytosol but alkalinizes it, as well. Cytoplasmic alkalinization is a vital process by insulin, which mechanism has not been studied in detail. The author believes that Insulin is one of the most important players in the regulation of intracellular pH (pHi), which, together with phosphate transport, is crucial for maintaining its anti-catabolic effect. Acidotic cytoplasm of the pancreas beta-cells increases while alkalotic decreases insulin secretion, which may be a feedback mechanism. 

  All insulin-mediated vital anabolic processes use energy derived from ATP. The impaired mitochondrial ATP production capability is a consequence of insulin resistance, which develops during the early stage of Metabolic Syndrome, and The chronic mental/social stress would exert its harmful psychosomatic effects through various clinical images of chronic low-grade hypercapnia (see Part 2). The author hypothesizes that impaired insulin-mediated phosphate transport is the primary cause of insulin resistance, which develops due to chronic hypercapnic acidosis. 

  Pi is a cytosolic signaling molecule, which can control the metabolic rate through its regulation of oxidative phosphorylation. Metabolic Syndrome and insulin resistance can persist for decades without a manifest of T2D. The author also assumes thatThe Decreased ATP productivity is compensated by increased lipid availability. Moderate persistent intracellular acidosis can induce T2D development - via vicious circles. ItT2D occurs when high triglyceride availability cannot compensate for insulin resistance and decreased ATP production alone. The guiding principle is that mitochondria have to provide near-normal ATP content at all costs in the cytoplasm of the cells; otherwise, the cell will be severely ill or killed. In order To increase ATP production, catabolism is ultimately raised enhanced. The liberated amino acids allow gluconeogenesis to proceed and raise serum glucose levels. (Pathophysiologically, hyperglycemia also has a compensatory role in ATP production, though toxic.) Insulin secretion is increased, and oral nutrient and calorie intake are also increased compensatorily. 

  Insulin is one of the most important of anabolic hormones. Type 2 Diabetes (T2D) is characterized by persistent, stealth catabolism, as well as impaired glucose and phosphate uptake. The phosphate transporting capability of insulin has been known for a long time, although it has been studied mainly since the 21^st century. According to the logic of the Momentary Intracellular Ion-Pattern Signaling, insulin should increase of HPO₄^2- in the cytosol - and does it, indeed. (It is not clear that this is a one- or multistep membrane-transport phenomenon.) Insulin does not only stimulate the transport of phosphate (Pi) into the cytosol but alkalinizes it, as well. Cytoplasmic alkalinization is a vital process by insulin, which mechanism has not been studied in detail. Insulin is one of the most important players in the regulation of intracellular pH, which, together with phosphate transport, is crucial for maintaining its anti-catabolic effect. Acidotic cytoplasm of the pancreas beta cells increases while alkalotic decreases insulin secretion, which may be a feedback mechanism. 

  All insulin-mediated vital anabolic processes use energy derived from ATP. The impaired mitochondrial ATP production capability is a consequence of insulin resistance, which develops during the early stage of Metabolic Syndrome, and can persist for decades without a manifest of T2D. Decreased ATP productivity is compensated by increased lipid availability. T2D develops when high triglyceride availability cannot compensate for insulin resistance and reduced ATP production. The guiding principle is that mitochondria have to provide near-normal ATP content at all costs in the cytoplasm of the cells; otherwise, the cells will be severely ill or killed. Catabolism rises to increase ATP production. The liberated amino acids allow gluconeogenesis to proceed and raise serum glucose levels. Pathophysiologically, both hyperglycemia and increased food uptake have compensatory roles in ATP production, though many vicious circles are generated.

Keywords: Chronic Low-Grade Hypercapnia; Cytosolic Alkalinization; Insulin Mediated Pi-Transport; Insulin Resistance; Intracellular Acidosis; Type 2 Diabetes

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Citation

Citation: András Sikter. “Psychosomatic Molecular Mechanisms of Metabolic Syndrome and Type 2 Diabetes. Part 3. Is Type 2 Diabetes a Decompensated Form of Metabolic Syndrome?". Acta Scientific Medical Sciences 4.3 (2020): 10-23.

Copyright

Copyright: © 2020 András Sikter. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.