Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions
The mitochondrial electron transport chain becomes overloaded in type 2 diabetes (T2D), which increases ROS (Reactive Oxygen Species) production and impairs mitochondrial function. Peripheral blood mononuclear cells (PBMCs) are critical players in the inflammatory process that underlies T2D. Poor gl...
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Elsevier
2025-04-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725000291 |
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| author | Julia Cacace Clara Luna-Marco Alberto Hermo-Argibay Catherine Pesantes-Somogyi Omar A. Hernández-López María Pelechá-Salvador Celia Bañuls Nadezda Apostolova Luis de Miguel-Rodríguez Carlos Morillas Milagros Rocha Susana Rovira-Llopis Víctor M. Víctor |
| author_facet | Julia Cacace Clara Luna-Marco Alberto Hermo-Argibay Catherine Pesantes-Somogyi Omar A. Hernández-López María Pelechá-Salvador Celia Bañuls Nadezda Apostolova Luis de Miguel-Rodríguez Carlos Morillas Milagros Rocha Susana Rovira-Llopis Víctor M. Víctor |
| author_sort | Julia Cacace |
| collection | DOAJ |
| description | The mitochondrial electron transport chain becomes overloaded in type 2 diabetes (T2D), which increases ROS (Reactive Oxygen Species) production and impairs mitochondrial function. Peripheral blood mononuclear cells (PBMCs) are critical players in the inflammatory process that underlies T2D. Poor glycaemic control in T2D is closely linked to the development of comorbidities.Our aim was to evaluate if glycaemic control in T2D has an impact on the oxygen consumption rates (OCR) of PBMC, OXPHOS complexes and inflammation.We recruited 181 subjects, consisting of 79 healthy controls, 64 patients with T2D and good glycaemic control (HbA1c<7 %), and 38 T2D patients with poor glycaemic control (HbA1c>7 %).We found a decrease in the basal OCR of PBMCs from patients with HbA1c>7 % with respect to controls (p < 0.05). Maximal OCR and spare respiratory capacity were lower in patients with HbA1c>7 % than in controls and patients with HbA1c<7 % (p < 0.05 for all). Mitochondrial ROS levels were higher in T2D patients, and particularly in the HbA1c > 7 group (p < 0.05 HbA1c<7 % vs control, p < 0.001 HbA1c>7 % vs control; p < 0.001 HbA1c > 7 vs HbA1c < 7). With respect to controls, poor glycaemic control in T2D patients was associated with a decrease in mitochondrial complex III and V (p < 0.05 and p < 0.01, respectively) and enhanced neutrophil-endothelial interactions (p < 0.001 vs controls). MPO levels were enhanced in T2D patients in general (p < 0.05 vs controls), and ICAM-1 and VCAM-1 were specifically increased in HbA1c > 7 patients vs controls (p < 0.01 and p < 0.001, respectively). Negative low-to-moderate correlations were found between HbA1c and basal respiration (r = −0.319, p < 0.05), maximal respiration (r = −0.350, p < 0.01) and spare respiratory capacity (r = −0.295, p < 0.05).Our findings suggest that poor glycaemic control during the progression of T2D compromises mitochondrial respiration and OXPHOS complex content in PBMCs. These alterations occur in parallel to enhanced neutrophil-endothelial interactions and adhesion molecule levels, leaving T2D patients with poor glycaemic control at a higher risk of developing vascular diseases. |
| format | Article |
| id | doaj-art-6df17bbdd5734a509dbe38f1fa6cf42f |
| institution | OA Journals |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
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| series | Redox Biology |
| spelling | doaj-art-6df17bbdd5734a509dbe38f1fa6cf42f2025-08-20T02:07:19ZengElsevierRedox Biology2213-23172025-04-018110351610.1016/j.redox.2025.103516Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactionsJulia Cacace0Clara Luna-Marco1Alberto Hermo-Argibay2Catherine Pesantes-Somogyi3Omar A. Hernández-López4María Pelechá-Salvador5Celia Bañuls6Nadezda Apostolova7Luis de Miguel-Rodríguez8Carlos Morillas9Milagros Rocha10Susana Rovira-Llopis11Víctor M. Víctor12Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, SpainService of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain; Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, SpainService of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, SpainService of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, SpainService of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, SpainService of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, SpainService of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, SpainNational Network of Biomedical Research on Hepatic and Digestive Diseases (CIBERehd), Valencia, Spain; Department of Pharmacology, University of Valencia, Valencia, SpainService of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, SpainService of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, SpainService of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain; National Network of Biomedical Research on Hepatic and Digestive Diseases (CIBERehd), Valencia, Spain; Corresponding author. Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Valencia, Spain.Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain; Corresponding author. Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Valencia, Spain.Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain; Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, Spain; National Network of Biomedical Research on Hepatic and Digestive Diseases (CIBERehd), Valencia, Spain; Corresponding author. Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, Spain.The mitochondrial electron transport chain becomes overloaded in type 2 diabetes (T2D), which increases ROS (Reactive Oxygen Species) production and impairs mitochondrial function. Peripheral blood mononuclear cells (PBMCs) are critical players in the inflammatory process that underlies T2D. Poor glycaemic control in T2D is closely linked to the development of comorbidities.Our aim was to evaluate if glycaemic control in T2D has an impact on the oxygen consumption rates (OCR) of PBMC, OXPHOS complexes and inflammation.We recruited 181 subjects, consisting of 79 healthy controls, 64 patients with T2D and good glycaemic control (HbA1c<7 %), and 38 T2D patients with poor glycaemic control (HbA1c>7 %).We found a decrease in the basal OCR of PBMCs from patients with HbA1c>7 % with respect to controls (p < 0.05). Maximal OCR and spare respiratory capacity were lower in patients with HbA1c>7 % than in controls and patients with HbA1c<7 % (p < 0.05 for all). Mitochondrial ROS levels were higher in T2D patients, and particularly in the HbA1c > 7 group (p < 0.05 HbA1c<7 % vs control, p < 0.001 HbA1c>7 % vs control; p < 0.001 HbA1c > 7 vs HbA1c < 7). With respect to controls, poor glycaemic control in T2D patients was associated with a decrease in mitochondrial complex III and V (p < 0.05 and p < 0.01, respectively) and enhanced neutrophil-endothelial interactions (p < 0.001 vs controls). MPO levels were enhanced in T2D patients in general (p < 0.05 vs controls), and ICAM-1 and VCAM-1 were specifically increased in HbA1c > 7 patients vs controls (p < 0.01 and p < 0.001, respectively). Negative low-to-moderate correlations were found between HbA1c and basal respiration (r = −0.319, p < 0.05), maximal respiration (r = −0.350, p < 0.01) and spare respiratory capacity (r = −0.295, p < 0.05).Our findings suggest that poor glycaemic control during the progression of T2D compromises mitochondrial respiration and OXPHOS complex content in PBMCs. These alterations occur in parallel to enhanced neutrophil-endothelial interactions and adhesion molecule levels, leaving T2D patients with poor glycaemic control at a higher risk of developing vascular diseases.http://www.sciencedirect.com/science/article/pii/S2213231725000291Type 2 diabetesHbA1cMitochondriaOXPHOSInflammation |
| spellingShingle | Julia Cacace Clara Luna-Marco Alberto Hermo-Argibay Catherine Pesantes-Somogyi Omar A. Hernández-López María Pelechá-Salvador Celia Bañuls Nadezda Apostolova Luis de Miguel-Rodríguez Carlos Morillas Milagros Rocha Susana Rovira-Llopis Víctor M. Víctor Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions Redox Biology Type 2 diabetes HbA1c Mitochondria OXPHOS Inflammation |
| title | Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions |
| title_full | Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions |
| title_fullStr | Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions |
| title_full_unstemmed | Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions |
| title_short | Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions |
| title_sort | poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate oxphos complex content and neutrophil endothelial interactions |
| topic | Type 2 diabetes HbA1c Mitochondria OXPHOS Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725000291 |
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