Benabdelkamel Hicham, Sebaa Rajaa, AlMalki Reem H, Masood Afshan, Alfadda Assim A, Abdel Rahman Anas M
Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia.
Saudi Pharm J. 2024 Nov;32(11):102172. doi: 10.1016/j.jsps.2024.102172. Epub 2024 Sep 12.
Liraglutide, a type2 diabetes mellitus (T2DM)-related treatment, improves glycemic control and reduces the risks of adverse cardiovascular events in T2DM patients. However, the underlying mechanisms of the above-mentioned beneficial effects of Liraglutide are not well understood. To have better understanding of these mechanisms, we aimed to study the metabolic impacts of Liraglutide on the metabolome and corresponding pathways in T2DM patients, especially metabolism plays a very fundamental role in health and diseases and is influenced by drugs. In this study, plasma samples collected from T2DM patients ( = 20) and taken pre- and post-Liraglutide treatment were used for untargeted metabolomics analyses, including metabolome profiling and metabolic pathway/network analyses. The metabolome profiling analyses identified 93 endogenous metabolites that were significantly affected by Liraglutide treatment where 49 and 44 metabolites were up and down regulated, respectively. Liraglutide caused metabolic alterations impacting metabolic pathways such as pentose and glucuronate interconversion and alanine, aspartate and glutamate metabolism in T2DM patients. Since the last-mentioned pathways are affected by Liraglutide, it could explain partially the overall beneficial effects of Liraglutide in T2DM, especially that glucuronate interconversion pathway is known by its important roles in eliminating toxic and undesirable substances from the human body to maintain good health status. In addition, the metabolism of amino acids induced by Liraglutide could improve the function of immune cells, strengthening the immunity of T2DM patients. Also, Liraglutide induced the level of other metabolites that help in the defense mechanism against oxidative events. Overall, the findings of this study provide a deeper understanding of the underlying mechanisms involved in the beneficial effects of Liraglutide in T2DM from the metabolic aspect.
利拉鲁肽是一种用于治疗2型糖尿病（T2DM）的药物，可改善血糖控制并降低T2DM患者发生不良心血管事件的风险。然而，利拉鲁肽上述有益作用的潜在机制尚不完全清楚。为了更好地理解这些机制，我们旨在研究利拉鲁肽对T2DM患者代谢组及相应代谢途径的影响，尤其是代谢在健康和疾病中起着非常重要的作用，且会受到药物的影响。在本研究中，收集了20例T2DM患者在利拉鲁肽治疗前后的血浆样本，用于非靶向代谢组学分析，包括代谢组图谱分析和代谢途径/网络分析。代谢组图谱分析确定了93种内源性代谢物受到利拉鲁肽治疗的显著影响，其中分别有49种和44种代谢物上调和下调。利拉鲁肽引起了代谢改变，影响了T2DM患者的代谢途径，如戊糖与葡糖醛酸相互转化以及丙氨酸、天冬氨酸和谷氨酸代谢。由于上述最后提到的途径受到利拉鲁肽的影响，这可以部分解释利拉鲁肽在T2DM中的总体有益作用，特别是葡糖醛酸相互转化途径因其在从人体中清除有毒和不良物质以维持良好健康状态方面的重要作用而为人所知。此外，利拉鲁肽诱导的氨基酸代谢可以改善免疫细胞的功能，增强T2DM患者的免疫力。同时，利拉鲁肽还诱导了其他有助于抗氧化防御机制的代谢物水平升高。总体而言，本研究结果从代谢方面更深入地理解了利拉鲁肽在T2DM中有益作用的潜在机制。
