Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin
<b>Background</b>: Obesity and type 2 diabetes mellitus (T2DM) are characterized by underlying low-grade chronic inflammation. Metformin has been used as the first line of therapy in T2DM as it decreases hepatic glucose production and glucose intestinal absorption, enhances insulin sensi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1345 |
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| author | Awad Alshahrani Ahmad Aljada Afshan Masood Muhammad Mujammami Assim A. Alfadda Mohthash Musambil Ibrahim O. Alanazi Mohammed Al Dubayee Anas M. Abdel Rahman Hicham Benabdelkamel |
| author_facet | Awad Alshahrani Ahmad Aljada Afshan Masood Muhammad Mujammami Assim A. Alfadda Mohthash Musambil Ibrahim O. Alanazi Mohammed Al Dubayee Anas M. Abdel Rahman Hicham Benabdelkamel |
| author_sort | Awad Alshahrani |
| collection | DOAJ |
| description | <b>Background</b>: Obesity and type 2 diabetes mellitus (T2DM) are characterized by underlying low-grade chronic inflammation. Metformin has been used as the first line of therapy in T2DM as it decreases hepatic glucose production and glucose intestinal absorption, enhances insulin sensitivity and weight loss, and is known to ameliorate inflammation. The mechanisms through which metformin exerts its effect remain unclear. Proteomics has emerged as a unique approach to explore the biological changes associated with diseases, including T2DM. It provides insight into the circulating biomarkers/mediators which could be utilized for disease screening, diagnosis, and prognosis. <b>Methods</b>: This study evaluated the proteomic changes in obese (Ob), obese diabetics (OD), and obese diabetic patients on metformin (ODM) using a 2D DIGE MALDI-TOF mass spectrometric approach. <b>Results</b>: Significant changes in sixteen plasma proteins (15 up and 1 down, ANOVA, <i>p</i> ≤ 0.05; fold change ≥ 1.5) were observed in the ODM group when compared to the Ob and OD groups. Bioinformatic network pathway analysis revealed that the majority of these altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. <b>Conclusions:</b> Our study provides important information about the possible biomarkers altered by metformin treatment in obese patients with and without T2DM. These altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. The presented proteomic profiling approach may help in identifying potential biomarkers/mediators affected by metformin treatment in T2DM and inform the understanding of metformin’s mechanisms of action. |
| first_indexed | 2024-03-10T20:58:22Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:58:22Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-10f1ca8ffe2a4a2d8d6ccbcf2b96eff12023-11-19T17:41:08ZengMDPI AGPharmaceuticals1424-82472023-09-011610134510.3390/ph16101345Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with MetforminAwad Alshahrani0Ahmad Aljada1Afshan Masood2Muhammad Mujammami3Assim A. Alfadda4Mohthash Musambil5Ibrahim O. Alanazi6Mohammed Al Dubayee7Anas M. Abdel Rahman8Hicham Benabdelkamel9Department of Medicine, Ministry of National Guard Health Affairs, Riyadh 11426, Saudi ArabiaDepartment of Biochemistry and Molecular Medicine, College of Medicine, Al Faisal University, Riyadh 11533, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi ArabiaEndocrinology and Diabetes Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi ArabiaHealthy Aging Research Institute, Health Sector, King Abdulaziz City for Science and Technology (KACST), P.O. Box 6086, Riyadh 11442, Saudi ArabiaDepartment of Medicine, Ministry of National Guard Health Affairs, Riyadh 11426, Saudi ArabiaDepartment of Biochemistry and Molecular Medicine, College of Medicine, Al Faisal University, Riyadh 11533, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia<b>Background</b>: Obesity and type 2 diabetes mellitus (T2DM) are characterized by underlying low-grade chronic inflammation. Metformin has been used as the first line of therapy in T2DM as it decreases hepatic glucose production and glucose intestinal absorption, enhances insulin sensitivity and weight loss, and is known to ameliorate inflammation. The mechanisms through which metformin exerts its effect remain unclear. Proteomics has emerged as a unique approach to explore the biological changes associated with diseases, including T2DM. It provides insight into the circulating biomarkers/mediators which could be utilized for disease screening, diagnosis, and prognosis. <b>Methods</b>: This study evaluated the proteomic changes in obese (Ob), obese diabetics (OD), and obese diabetic patients on metformin (ODM) using a 2D DIGE MALDI-TOF mass spectrometric approach. <b>Results</b>: Significant changes in sixteen plasma proteins (15 up and 1 down, ANOVA, <i>p</i> ≤ 0.05; fold change ≥ 1.5) were observed in the ODM group when compared to the Ob and OD groups. Bioinformatic network pathway analysis revealed that the majority of these altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. <b>Conclusions:</b> Our study provides important information about the possible biomarkers altered by metformin treatment in obese patients with and without T2DM. These altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. The presented proteomic profiling approach may help in identifying potential biomarkers/mediators affected by metformin treatment in T2DM and inform the understanding of metformin’s mechanisms of action.https://www.mdpi.com/1424-8247/16/10/1345metforminproteomicsobesitytype 2 diabetes mellitusmass spectrometry |
| spellingShingle | Awad Alshahrani Ahmad Aljada Afshan Masood Muhammad Mujammami Assim A. Alfadda Mohthash Musambil Ibrahim O. Alanazi Mohammed Al Dubayee Anas M. Abdel Rahman Hicham Benabdelkamel Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin Pharmaceuticals metformin proteomics obesity type 2 diabetes mellitus mass spectrometry |
| title | Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin |
| title_full | Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin |
| title_fullStr | Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin |
| title_full_unstemmed | Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin |
| title_short | Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin |
| title_sort | proteomic profiling identifies distinct regulation of proteins in obese diabetic patients treated with metformin |
| topic | metformin proteomics obesity type 2 diabetes mellitus mass spectrometry |
| url | https://www.mdpi.com/1424-8247/16/10/1345 |
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