Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus

Various important transcription factors in the pancreas are involved in the process of pancreas development, the differentiation of endocrine progenitor cells into mature insulin-producing pancreatic beta-cells and the preservation of mature beta-cell function. However, when beta-cells are continuously exposed to a high glucose concentration for a long period of time, the expression levels of several insulin gene transcription factors are substantially suppressed, which finally leads to pancreatic beta-cell failure found in type 2 diabetes mellitus. Here we show the possible underlying pathway for beta-cell failure. It is likely that reduced expression levels of MafA and PDX-1 and/or incretin receptor in beta-cells are closely associated with beta-cell failure in type 2 diabetes mellitus. Additionally, since incretin receptor expression is reduced in the advanced stage of diabetes mellitus, incretin-based medicines show more favorable effects against beta-cell failure, especially in the early stage of diabetes mellitus compared to the advanced stage. On the other hand, many subjects have recently suffered from life-threatening coronavirus infection, and coronavirus infection has brought about a new and persistent pandemic. Additionally, the spread of coronavirus infection has led to various limitations on the activities of daily life and has restricted economic development worldwide. It has been reported recently that SARS-CoV-2 directly infects beta-cells through neuropilin-1, leading to apoptotic beta-cell death and a reduction in insulin secretion. In this review article, we feature a possible molecular mechanism for pancreatic beta-cell failure, which is often observed in type 2 diabetes mellitus. Finally, we are hopeful that coronavirus infection will decline and normal daily life will soon resume all over the world.

Automated summary

Various transcription factors in the pancreas play important roles in pancreas development, differentiation of endocrine progenitor cells, and preservation of mature beta-cell function. In type 2 diabetes mellitus, the expression levels of insulin gene transcription factors are suppressed due to prolonged exposure to high glucose levels, leading to beta-cell failure. In addition, coronavirus infection directly infects beta-cells, causing cell death and reduced insulin secretion.