Department of Medicine, College of Medicine and King Saud Medical City, King Saud University, Riyadh, Saudi Arabia.
Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Diab Vasc Dis Res. 2022 May-Jun;19(3):14791641221094322. doi: 10.1177/14791641221094322.
Diabetes mellitus is a chronic multisystem disease with a high global prevalence, including in Saudi Arabia. The Glucagon-like Peptide (GLP-1) receptor agonist liraglutide is known to lower glucose levels, reduce weight and improve cardiovascular outcome. However, mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear.
In the present study, a 2D-DIGE MALDI-TOF mass spectrometric approach combined with bioinformatics and network pathway analysis explore the plasma proteomic profile. The study involved 20 patients with T2DM with mean age of 54.4 ± 9.5 years and Hemoglobin A1c (HbA1c) between 8% and 11% (inclusive).
A statistically significant change ( < .006) was observed in HbA1c with no significant changes in body weight, renal function, or markers of dyslipidemia post-treatment with liraglutide. 2 D-DIGE gel analysis identified significant changes (⩾1.5-fold change, Analysis of variance (ANOVA), ⩽ 0.05) in 72 proteins, (62 down and 10 up) in liraglutide pre-treatment compared to the post-treatment state. Proteins identified in our study were found to regulate metabolic processes including acute phase response proteins, enzymes, apolipoproteins with involvement of the inflammatory signaling pathways, NF-κB, AKT, and p38 MAPK.
Liraglutide treatment decreased levels of acute phase response that to reduce the systemic chronic inflammatory state and oxidative stress, and eventually improve the cardio-metabolic profile in these patients.
糖尿病是一种慢性多系统疾病，具有很高的全球患病率，包括在沙特阿拉伯。胰高血糖素样肽 (GLP-1) 受体激动剂利拉鲁肽已知可降低血糖水平、减轻体重并改善心血管结局。然而，利拉鲁肽治疗 2 型糖尿病 (T2DM) 患者的获益机制尚不清楚。
在本研究中，采用 2D-DIGE MALDI-TOF 质谱联用技术结合生物信息学和网络通路分析方法探索血浆蛋白质组谱。该研究纳入了 20 名 T2DM 患者，平均年龄为 54.4±9.5 岁，糖化血红蛋白 (HbA1c) 在 8%至 11%之间（包括 8%和 11%）。
与治疗前相比，利拉鲁肽治疗后 HbA1c 有统计学意义的变化（<0.006），体重、肾功能或血脂异常标志物无显著变化。2D-DIGE 凝胶分析发现，利拉鲁肽治疗前与治疗后相比，有 72 种蛋白质发生了显著变化（≥1.5 倍变化，方差分析（ANOVA），<0.05），其中 62 种下调，10 种上调。我们研究中鉴定的蛋白质被发现调节代谢过程，包括急性期反应蛋白、酶、载脂蛋白，涉及炎症信号通路、NF-κB、AKT 和 p38 MAPK。
利拉鲁肽治疗降低了急性期反应蛋白的水平，从而减轻了全身慢性炎症状态和氧化应激，最终改善了这些患者的心脏代谢状况。
