Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, I.R. Iran.
Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Curr Mol Pharmacol. 2023;16(4):448-464. doi: 10.2174/1874467215666220829102020.
The increasing number of cases of diabetes mellitus (DM) and related diseases has become a global health concern. In this context, controlling blood glucose levels is critical to prevent and/or slow down the development of diabetes-related complications. Incretins, as gutderived hormones that trigger the post-meal secretion of insulin, are a well-known family of blood glucose modulators. Currently, incretin medications, including glucagon-like peptide-1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors, are extensively used to treat patients with type 2 diabetes mellitus (T2D). Several experimental and clinical studies illustrate that these metabolic hormones exert their antidiabetic effects through multiple molecular mechanisms. Accordingly, the current review aims to investigate key mechanisms and signaling pathways, such as the cAMP/PKA, Nrf2, PI3K/Akt, and AMPK pathways, associated with the antidiabetic effects of incretins. It also summarizes the outcomes of a group of clinical trials evaluating the incretins' antidiabetic potential in diabetic patients.
糖尿病（DM）和相关疾病的病例不断增加，已成为全球关注的健康问题。在这种情况下，控制血糖水平对于预防和/或减缓糖尿病相关并发症的发展至关重要。肠促胰岛素是一类已知的血糖调节剂，作为源自肠道的激素，可触发餐后胰岛素分泌。目前，胰高血糖素样肽-1 受体激动剂（GLP-1RA）和二肽基肽酶-4（DPP-4）抑制剂等肠促胰岛素类药物被广泛用于治疗 2 型糖尿病（T2D）患者。多项实验和临床研究表明，这些代谢激素通过多种分子机制发挥其抗糖尿病作用。因此，本综述旨在研究与肠促胰岛素的抗糖尿病作用相关的关键机制和信号通路，如 cAMP/PKA、Nrf2、PI3K/Akt 和 AMPK 通路。还总结了一组评估肠促胰岛素在糖尿病患者中抗糖尿病潜力的临床试验的结果。
