A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation
Systemic inflammation is related to hyperglycemia in diabetes mellitus (DM). C-C chemokine motif ligand (CCL) 4 is upregulated in type 1 & type 2 DM patients. This study aimed to investigate if CCL4 could be a potential target to improve blood sugar control in different experimental DM model...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.650626/full |
| _version_ | 1818458690762571776 |
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| author | Ting-Ting Chang Ting-Ting Chang Ting-Ting Chang Liang-Yu Lin Liang-Yu Lin Jaw-Wen Chen Jaw-Wen Chen Jaw-Wen Chen Jaw-Wen Chen Jaw-Wen Chen |
| author_facet | Ting-Ting Chang Ting-Ting Chang Ting-Ting Chang Liang-Yu Lin Liang-Yu Lin Jaw-Wen Chen Jaw-Wen Chen Jaw-Wen Chen Jaw-Wen Chen Jaw-Wen Chen |
| author_sort | Ting-Ting Chang |
| collection | DOAJ |
| description | Systemic inflammation is related to hyperglycemia in diabetes mellitus (DM). C-C chemokine motif ligand (CCL) 4 is upregulated in type 1 & type 2 DM patients. This study aimed to investigate if CCL4 could be a potential target to improve blood sugar control in different experimental DM models. Streptozotocin-induced diabetic mice, Leprdb/JNarl diabetic mice, and C57BL/6 mice fed a high fat diet were used as the type 1 DM, type 2 DM, and metabolic syndrome model individually. Mice were randomly assigned to receive an anti-CCL4 neutralizing monoclonal antibody. The pancreatic β-cells were treated with streptozotocin for in vitro experiments. In streptozotocin-induced diabetic mice, inhibition of CCL4 controlled blood sugar, increased serum insulin levels, increased islet cell proliferation and decreased pancreatic interleukin (IL)-6 expression. In the type 2 diabetes and metabolic syndrome models, CCL4 inhibition retarded the progression of hyperglycemia, reduced serum tumor necrosis factor (TNF)-α and IL-6 levels, and improved insulin resistance via reducing the phosphorylation of insulin receptor substrate-1 in skeletal muscle and liver tissues. CCL4 inhibition directly protected pancreatic β-cells from streptozotocin stimulation. Furthermore, CCL4-induced IL-6 and TNF-α expressions could be abolished by siRNA of CCR2/CCR5. In summary, direct inhibition of CCL4 protected pancreatic islet cells, improved insulin resistance and retarded the progression of hyperglycemia in different experimental models, suggesting the critical role of CCL4-related inflammation in the progression of DM. Future experiments may investigate if CCL4 could be a potential target for blood sugar control in clinical DM. |
| first_indexed | 2024-12-14T23:02:28Z |
| format | Article |
| id | doaj.art-6f764ec3b1464a869c0380a405521ca6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T23:02:28Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6f764ec3b1464a869c0380a405521ca62022-12-21T22:44:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.650626650626A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating InflammationTing-Ting Chang0Ting-Ting Chang1Ting-Ting Chang2Liang-Yu Lin3Liang-Yu Lin4Jaw-Wen Chen5Jaw-Wen Chen6Jaw-Wen Chen7Jaw-Wen Chen8Jaw-Wen Chen9Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, TaiwanDepartment and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanDivision of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanDepartment and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, TaiwanDepartment and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, TaiwanHealthcare and Services Center, Taipei Veterans General Hospital, Taipei, TaiwanDivision of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanCardiovascular Research Center, National Yang-Ming University, Taipei, TaiwanSystemic inflammation is related to hyperglycemia in diabetes mellitus (DM). C-C chemokine motif ligand (CCL) 4 is upregulated in type 1 & type 2 DM patients. This study aimed to investigate if CCL4 could be a potential target to improve blood sugar control in different experimental DM models. Streptozotocin-induced diabetic mice, Leprdb/JNarl diabetic mice, and C57BL/6 mice fed a high fat diet were used as the type 1 DM, type 2 DM, and metabolic syndrome model individually. Mice were randomly assigned to receive an anti-CCL4 neutralizing monoclonal antibody. The pancreatic β-cells were treated with streptozotocin for in vitro experiments. In streptozotocin-induced diabetic mice, inhibition of CCL4 controlled blood sugar, increased serum insulin levels, increased islet cell proliferation and decreased pancreatic interleukin (IL)-6 expression. In the type 2 diabetes and metabolic syndrome models, CCL4 inhibition retarded the progression of hyperglycemia, reduced serum tumor necrosis factor (TNF)-α and IL-6 levels, and improved insulin resistance via reducing the phosphorylation of insulin receptor substrate-1 in skeletal muscle and liver tissues. CCL4 inhibition directly protected pancreatic β-cells from streptozotocin stimulation. Furthermore, CCL4-induced IL-6 and TNF-α expressions could be abolished by siRNA of CCR2/CCR5. In summary, direct inhibition of CCL4 protected pancreatic islet cells, improved insulin resistance and retarded the progression of hyperglycemia in different experimental models, suggesting the critical role of CCL4-related inflammation in the progression of DM. Future experiments may investigate if CCL4 could be a potential target for blood sugar control in clinical DM.https://www.frontiersin.org/articles/10.3389/fimmu.2021.650626/fullblood sugarC-C chemokine motif ligand 4diabetes mellitusinflammationinsulin resistancepancreatic islet cells |
| spellingShingle | Ting-Ting Chang Ting-Ting Chang Ting-Ting Chang Liang-Yu Lin Liang-Yu Lin Jaw-Wen Chen Jaw-Wen Chen Jaw-Wen Chen Jaw-Wen Chen Jaw-Wen Chen A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation Frontiers in Immunology blood sugar C-C chemokine motif ligand 4 diabetes mellitus inflammation insulin resistance pancreatic islet cells |
| title | A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation |
| title_full | A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation |
| title_fullStr | A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation |
| title_full_unstemmed | A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation |
| title_short | A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation |
| title_sort | novel resolution of diabetes c c chemokine motif ligand 4 is a common target in different types of diabetes by protecting pancreatic islet cell and modulating inflammation |
| topic | blood sugar C-C chemokine motif ligand 4 diabetes mellitus inflammation insulin resistance pancreatic islet cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.650626/full |
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