2020 年 7 巻 1 号 p. 13-21
Glycative stress causes post-translational modifications of protein at the molecular level and increases the risks of various aging-related diseases, such as diabetic complications. There are two representative processes of the unphysiological protein modifications, i.e. (1) the carbonylation caused by aldehyde derived from glucose and lipids and the formation of advanced glycation end products (AGEs), and (2) cysteine succination derived from a disorder of the TCA cycle. Endoplasmic reticulum (ER) stress increases in pancreatic β-cells due to the formation of AGEs caused by glycative stress, and causes a reduction in insulin secretion. Lysine and arginine in amino acid sequence of insulin are susceptible to carbonyl modification and are resistant against the enzyme reaction to insulin from proinsulin. As a result, insulin synthetic quantity decreases. Approximately 9% of insulin in serum of patients with diabetes becomes glycated insulin, and it causes the patient’s insulin resistance. These findings show that glycative stress is involved not only in diabetic complications, but also the onset and development of diabetes. It has also become clear that there is a “vicious cycle” to increase the onset of diseases caused by glycative stress. Similarly, “vicious cycles” also exist through visceral fat, kidney and skeletal muscles. Recently the diseases caused by glycative stress are increasing worldwide. In order to prevent the onset and development of these diseases related to glycative stress, it is important to (1) implement countermeasures against glycative stress at an early stage and (2) understand the mechanisms of these vicious cycles and prevent them.
