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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Main Authors: Mohamed Rafiullah, Hicham Benabdelkamel, Afshan Masood, Aishah A. Ekhzaimy, Mohthash Musambil, Salini Scaria Joy, Assim A. Alfadda
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/45/2/92
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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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