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 β-cells and the preservation of mature β-cell function. However, when β-cells are continuously expos...
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MDPI AG
2022-03-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/4/818 |
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| author | Hideaki Kaneto Tomohiko Kimura Masashi Shimoda Atsushi Obata Junpei Sanada Yoshiro Fushimi Taka-aki Matsuoka Kohei Kaku |
| author_facet | Hideaki Kaneto Tomohiko Kimura Masashi Shimoda Atsushi Obata Junpei Sanada Yoshiro Fushimi Taka-aki Matsuoka Kohei Kaku |
| author_sort | Hideaki Kaneto |
| collection | DOAJ |
| description | 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 β-cells and the preservation of mature β-cell function. However, when β-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 β-cell failure found in type 2 diabetes mellitus. Here we show the possible underlying pathway for β-cell failure. It is likely that reduced expression levels of MafA and PDX-1 and/or incretin receptor in β-cells are closely associated with β-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 β-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 β-cells through neuropilin-1, leading to apoptotic β-cell death and a reduction in insulin secretion. In this review article, we feature a possible molecular mechanism for pancreatic β-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. |
| first_indexed | 2024-03-09T11:07:12Z |
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| id | doaj.art-7673f96664b341128bbb1881f3377d4a |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T11:07:12Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-7673f96664b341128bbb1881f3377d4a2023-12-01T00:53:48ZengMDPI AGBiomedicines2227-90592022-03-0110481810.3390/biomedicines10040818Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes MellitusHideaki Kaneto0Tomohiko Kimura1Masashi Shimoda2Atsushi Obata3Junpei Sanada4Yoshiro Fushimi5Taka-aki Matsuoka6Kohei Kaku7Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, JapanThe First Department of Internal Medicine, Wakayama Medical University, 811-1 Kiimidera, Wakayama 641-8509, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, JapanVarious 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 β-cells and the preservation of mature β-cell function. However, when β-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 β-cell failure found in type 2 diabetes mellitus. Here we show the possible underlying pathway for β-cell failure. It is likely that reduced expression levels of MafA and PDX-1 and/or incretin receptor in β-cells are closely associated with β-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 β-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 β-cells through neuropilin-1, leading to apoptotic β-cell death and a reduction in insulin secretion. In this review article, we feature a possible molecular mechanism for pancreatic β-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.https://www.mdpi.com/2227-9059/10/4/818PDX-1MafAincretin reeceptorGLP-1 receptor activatorcoronavirus infection |
| spellingShingle | Hideaki Kaneto Tomohiko Kimura Masashi Shimoda Atsushi Obata Junpei Sanada Yoshiro Fushimi Taka-aki Matsuoka Kohei Kaku Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus Biomedicines PDX-1 MafA incretin reeceptor GLP-1 receptor activator coronavirus infection |
| title | Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus |
| title_full | Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus |
| title_fullStr | Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus |
| title_full_unstemmed | Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus |
| title_short | Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus |
| title_sort | molecular mechanism of pancreatic β cell failure in type 2 diabetes mellitus |
| topic | PDX-1 MafA incretin reeceptor GLP-1 receptor activator coronavirus infection |
| url | https://www.mdpi.com/2227-9059/10/4/818 |
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