Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System
Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription fa...
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Korean Diabetes Association
2025-01-01
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| Series: | Diabetes & Metabolism Journal |
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| Online Access: | http://e-dmj.org/upload/pdf/dmj-2024-0796.pdf |
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| author | Il Rae Park Yong Geun Chung Kyu Chang Won |
| author_facet | Il Rae Park Yong Geun Chung Kyu Chang Won |
| author_sort | Il Rae Park |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation. Targeting CD36 pathways has emerged as a promising therapeutic strategy. Oral hypoglycemic agents, such as metformin, teneligliptin, and pioglitazone, have shown protective effects on β-cells by enhancing antioxidant defenses. These agents reduce glucotoxicity via mechanisms such as suppressing CD36 expression and stabilizing mitochondrial function. Additionally, novel insights into the glutathione antioxidant system and its role in β-cell survival underscore its therapeutic potential. This review focuses on the key contribution of oxidative stress and CD36 to β-cell impairment, the therapeutic promise of antioxidants, and the need for further research to apply these findings in clinical practice. Promising strategies targeting these mechanisms may help preserve β-cell function and slow T2DM progression. |
| format | Article |
| id | doaj-art-a52881d6972c42d4b604cd1cf37843de |
| institution | DOAJ |
| issn | 2233-6079 2233-6087 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Korean Diabetes Association |
| record_format | Article |
| series | Diabetes & Metabolism Journal |
| spelling | doaj-art-a52881d6972c42d4b604cd1cf37843de2025-08-20T02:41:07ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872025-01-0149111210.4093/dmj.2024.07962906Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant SystemIl Rae Park0Yong Geun Chung1Kyu Chang Won Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, KoreaType 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation. Targeting CD36 pathways has emerged as a promising therapeutic strategy. Oral hypoglycemic agents, such as metformin, teneligliptin, and pioglitazone, have shown protective effects on β-cells by enhancing antioxidant defenses. These agents reduce glucotoxicity via mechanisms such as suppressing CD36 expression and stabilizing mitochondrial function. Additionally, novel insights into the glutathione antioxidant system and its role in β-cell survival underscore its therapeutic potential. This review focuses on the key contribution of oxidative stress and CD36 to β-cell impairment, the therapeutic promise of antioxidants, and the need for further research to apply these findings in clinical practice. Promising strategies targeting these mechanisms may help preserve β-cell function and slow T2DM progression.http://e-dmj.org/upload/pdf/dmj-2024-0796.pdfcd36 antigensdiabetes mellitus, type 2hyperglycemiainsulin-secreting cellsoxidative stressreactive oxygen species |
| spellingShingle | Il Rae Park Yong Geun Chung Kyu Chang Won Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System Diabetes & Metabolism Journal cd36 antigens diabetes mellitus, type 2 hyperglycemia insulin-secreting cells oxidative stress reactive oxygen species |
| title | Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System |
| title_full | Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System |
| title_fullStr | Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System |
| title_full_unstemmed | Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System |
| title_short | Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System |
| title_sort | overcoming β cell dysfunction in type 2 diabetes mellitus cd36 inhibition and antioxidant system |
| topic | cd36 antigens diabetes mellitus, type 2 hyperglycemia insulin-secreting cells oxidative stress reactive oxygen species |
| url | http://e-dmj.org/upload/pdf/dmj-2024-0796.pdf |
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