Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells
The dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is essential f...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/12/9/1228 |
| _version_ | 1827663071612502016 |
|---|---|
| author | Eri Mukai Shimpei Fujimoto Nobuya Inagaki |
| author_facet | Eri Mukai Shimpei Fujimoto Nobuya Inagaki |
| author_sort | Eri Mukai |
| collection | DOAJ |
| description | The dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is essential for insulin secretion. High glucose metabolism for insulin secretion generates reactive oxygen species (ROS) in mitochondria. In addition, the expression of antioxidant enzymes is very low in β-cells. Therefore, β-cells are easily exposed to oxidative stress. In islet studies using a nonobese T2DM animal model that exhibits selective impairment of glucose-induced insulin secretion (GSIS), quenching ROS generated by glucose stimulation and accumulated under glucose toxicity can improve impaired GSIS. Acute ROS generation and toxicity cause glucose metabolism disorders through different molecular mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, is a master regulator of antioxidant defense and a potential therapeutic target in oxidative stress-related diseases, suggesting the possible involvement of Nrf2 in β-cell dysfunction caused by ROS. In this review, we describe the mechanisms of insulin secretory defects induced by oxidative stress in diabetic β-cells. |
| first_indexed | 2024-03-10T00:37:36Z |
| format | Article |
| id | doaj.art-c773393b74584e77afc9a431c66ce946 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T00:37:36Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-c773393b74584e77afc9a431c66ce9462023-11-23T15:15:02ZengMDPI AGBiomolecules2218-273X2022-09-01129122810.3390/biom12091228Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-CellsEri Mukai0Shimpei Fujimoto1Nobuya Inagaki2Medical Physiology and Metabolism Laboratory, Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu 5258577, JapanDepartment of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University, Kochi 7838505, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 6068507, JapanThe dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is essential for insulin secretion. High glucose metabolism for insulin secretion generates reactive oxygen species (ROS) in mitochondria. In addition, the expression of antioxidant enzymes is very low in β-cells. Therefore, β-cells are easily exposed to oxidative stress. In islet studies using a nonobese T2DM animal model that exhibits selective impairment of glucose-induced insulin secretion (GSIS), quenching ROS generated by glucose stimulation and accumulated under glucose toxicity can improve impaired GSIS. Acute ROS generation and toxicity cause glucose metabolism disorders through different molecular mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, is a master regulator of antioxidant defense and a potential therapeutic target in oxidative stress-related diseases, suggesting the possible involvement of Nrf2 in β-cell dysfunction caused by ROS. In this review, we describe the mechanisms of insulin secretory defects induced by oxidative stress in diabetic β-cells.https://www.mdpi.com/2218-273X/12/9/1228reactive oxygen speciespancreatic β-cellsinsulin secretionglucose metabolismoxidative stress |
| spellingShingle | Eri Mukai Shimpei Fujimoto Nobuya Inagaki Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells Biomolecules reactive oxygen species pancreatic β-cells insulin secretion glucose metabolism oxidative stress |
| title | Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells |
| title_full | Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells |
| title_fullStr | Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells |
| title_full_unstemmed | Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells |
| title_short | Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells |
| title_sort | role of reactive oxygen species in glucose metabolism disorder in diabetic pancreatic β cells |
| topic | reactive oxygen species pancreatic β-cells insulin secretion glucose metabolism oxidative stress |
| url | https://www.mdpi.com/2218-273X/12/9/1228 |
| work_keys_str_mv | AT erimukai roleofreactiveoxygenspeciesinglucosemetabolismdisorderindiabeticpancreaticbcells AT shimpeifujimoto roleofreactiveoxygenspeciesinglucosemetabolismdisorderindiabeticpancreaticbcells AT nobuyainagaki roleofreactiveoxygenspeciesinglucosemetabolismdisorderindiabeticpancreaticbcells |