Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment
Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diab...
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MDPI AG
2023-02-01
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author | Mohamed Rafiullah Hicham Benabdelkamel Afshan Masood Aishah A. Ekhzaimy Mohthash Musambil Salini Scaria Joy Assim A. Alfadda |
author_facet | Mohamed Rafiullah Hicham Benabdelkamel Afshan Masood Aishah A. Ekhzaimy Mohthash Musambil Salini Scaria Joy Assim A. Alfadda |
author_sort | Mohamed Rafiullah |
collection | DOAJ |
description | Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. Twelve male patients with T2DM (pre and post liraglutide treatment) and HbA1c between 8% and 11% were recruited. In the present study, a two-dimensional difference gel electrophoresis (2D-DIGE) matrix-assisted laser desorption/ionization-time of flight (MALDI TOF) mass spectrometric approach combined with bioinformatics and network pathway analysis was used to explore the urine proteomic profile. The mean age of the patients was 52.4 ± 7.5 years. After treatment with liraglutide, a statistically significant change (<i>p</i> < 0.006) was observed in HbA1c with no significant changes in body weight or markers of dyslipidemia. Two-dimensional difference gel electrophoresis identified significant changes (≥1.5-fold change, ANOVA, <i>p</i> ≤ 0.05) in 32 proteins (4 down- and 28 upregulated) in liraglutide post treatment compared to the pre-treatment state. Albumin, serotransferrin, metallothionein-2 (MT-2), and keratins K1 and K10 were found to be upregulated after liraglutide treatment. The patients showed significant improvement in glycemic control after the 12-week treatment with liraglutide. The renoprotective effect of liraglutide may be linked to the increased urinary abundance of MT-2 and the decreased abundance of zinc alpha 2-glycoprotein (ZAG) and Alpha-1 antitrypsin (α1-AT). More studies are needed to elucidate the molecular mechanisms behind the renoprotective effects of liraglutide. |
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spelling | doaj.art-f3eb8dcc9c35436cab0a607e6c7ed7e32023-11-16T19:51:00ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-02-014521407142110.3390/cimb45020092Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide TreatmentMohamed Rafiullah0Hicham Benabdelkamel1Afshan Masood2Aishah A. Ekhzaimy3Mohthash Musambil4Salini Scaria Joy5Assim A. Alfadda6Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh 12211, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 12211, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 12211, Saudi ArabiaDepartment of Medicine, College of Medicine, King Saud University, Riyadh 12211, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 12211, Saudi ArabiaStrategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh 12211, Saudi ArabiaStrategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh 12211, Saudi ArabiaDiabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. Twelve male patients with T2DM (pre and post liraglutide treatment) and HbA1c between 8% and 11% were recruited. In the present study, a two-dimensional difference gel electrophoresis (2D-DIGE) matrix-assisted laser desorption/ionization-time of flight (MALDI TOF) mass spectrometric approach combined with bioinformatics and network pathway analysis was used to explore the urine proteomic profile. The mean age of the patients was 52.4 ± 7.5 years. After treatment with liraglutide, a statistically significant change (<i>p</i> < 0.006) was observed in HbA1c with no significant changes in body weight or markers of dyslipidemia. Two-dimensional difference gel electrophoresis identified significant changes (≥1.5-fold change, ANOVA, <i>p</i> ≤ 0.05) in 32 proteins (4 down- and 28 upregulated) in liraglutide post treatment compared to the pre-treatment state. Albumin, serotransferrin, metallothionein-2 (MT-2), and keratins K1 and K10 were found to be upregulated after liraglutide treatment. The patients showed significant improvement in glycemic control after the 12-week treatment with liraglutide. The renoprotective effect of liraglutide may be linked to the increased urinary abundance of MT-2 and the decreased abundance of zinc alpha 2-glycoprotein (ZAG) and Alpha-1 antitrypsin (α1-AT). More studies are needed to elucidate the molecular mechanisms behind the renoprotective effects of liraglutide.https://www.mdpi.com/1467-3045/45/2/92GLP-1 receptors agonistliraglutidemetallothionein-2proteomicstype 2 diabetes mellituszinc-alpha-2-glycoprotein |
spellingShingle | Mohamed Rafiullah Hicham Benabdelkamel Afshan Masood Aishah A. Ekhzaimy Mohthash Musambil Salini Scaria Joy Assim A. Alfadda Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment Current Issues in Molecular Biology GLP-1 receptors agonist liraglutide metallothionein-2 proteomics type 2 diabetes mellitus zinc-alpha-2-glycoprotein |
title | Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment |
title_full | Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment |
title_fullStr | Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment |
title_full_unstemmed | Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment |
title_short | Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment |
title_sort | urinary proteome differences in patients with type 2 diabetes pre and post liraglutide treatment |
topic | GLP-1 receptors agonist liraglutide metallothionein-2 proteomics type 2 diabetes mellitus zinc-alpha-2-glycoprotein |
url | https://www.mdpi.com/1467-3045/45/2/92 |
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