Al-Noshokaty Tohada M, Abdelhamid Rehab, Abdelmaksoud Nourhan M, Khaled Aya, Hossam Mariam, Ahmed Razan, Saber Toka, Khaled Shahd, Elshaer Shereen Saeid, Abulsoud Ahmed I
Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt.
Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, Egypt.
Toxicol Rep. 2025 Jan 16;14:101895. doi: 10.1016/j.toxrep.2025.101895. eCollection 2025 Jun.
Glucagon (GCG) like peptide 1 (GLP-1) has emerged as a powerful player in regulating metabolism and a promising therapeutic target for various chronic diseases. This review delves into the physiological roles of GLP-1, exploring its impact on glucose homeostasis, insulin secretion, and satiety. We examine the compelling evidence supporting GLP-1 receptor agonists (GLP-1RAs) in managing type 2 diabetes (T2D), obesity, and other diseases. The intricate molecular mechanisms underlying GLP-1RAs are explored, including their interactions with pathways like extracellular signal-regulated kinase 1/2 (ERK1/2), activated protein kinase (AMPK), cyclic adenine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Expanding our understanding, the review investigates the potential role of GLP-1 in cancers. Also, microribonucleic acid (RNA) (miRNAs), critical regulators of gene expression, are introduced as potential modulators of GLP-1 signaling. We delve into the link between miRNAs and T2D obesity and explore specific miRNA examples influencing GLP-1R function. Finally, the review explores the rationale for seeking alternatives to GLP-1RAs and highlights natural products with promising GLP-1 modulatory effects.
胰高血糖素样肽1(GLP-1)已成为调节新陈代谢的重要因子以及多种慢性疾病颇具前景的治疗靶点。本综述深入探讨了GLP-1的生理作用,探究其对葡萄糖稳态、胰岛素分泌和饱腹感的影响。我们研究了支持GLP-1受体激动剂(GLP-1RAs)用于治疗2型糖尿病(T2D)、肥胖症及其他疾病的有力证据。探讨了GLP-1RAs背后复杂的分子机制,包括它们与细胞外信号调节激酶1/2(ERK1/2)、激活蛋白激酶(AMPK)、环磷酸腺苷(cAMP)、丝裂原活化蛋白激酶(MAPK)和蛋白激酶C(PKC)等信号通路的相互作用。为拓展认识,本综述研究了GLP-1在癌症中的潜在作用。此外,还介绍了作为GLP-1信号潜在调节剂的微小核糖核酸(miRNA),它是基因表达的关键调节因子。我们深入探讨了miRNA与T2D肥胖症之间的联系,并探究了影响GLP-1R功能的特定miRNA实例。最后,本综述探讨了寻求GLP-1RAs替代物的基本原理,并重点介绍了具有前景的GLP-1调节作用的天然产物。