Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Medical School, Nantong University, Nantong, China.
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, China.
CNS Neurosci Ther. 2024 Jun;30(6):e14806. doi: 10.1111/cns.14806.
Glucose-dependent insulinotropic polypeptide (GIP) is a ligand of glucose-dependent insulinotropic polypeptide receptor (GIPR) that plays an important role in the digestive system. In recent years, GIP has been regarded as a hormone-like peptide to regulate the local metabolic environment. In this study, we investigated the antioxidant role of GIP on the neuron and explored the possible mechanism.
Cell counting Kit-8 (CCK-8) was used to measure cell survival. TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect apoptosis in vitro and in vivo. Reactive oxygen species (ROS) levels were probed with 2', 7'-Dichloro dihydrofluorescein diacetate (DCFH-DA), and glucose intake was detected with 2-NBDG. Immunofluorescence staining and western blot were used to evaluate the protein level in cells and tissues. Hematoxylin-eosin (HE) staining, immunofluorescence staining and tract-tracing were used to observe the morphology of the injured spinal cord. Basso-Beattie-Bresnahan (BBB) assay was used to evaluate functional recovery after spinal cord injury.
GIP reduced the ROS level and protected cells from apoptosis in cultured neurons and injured spinal cord. GIP facilitated wound healing and functional recovery of the injured spinal cord. GIP significantly improved the glucose uptake of cultured neurons. Meanwhile, inhibition of glucose uptake significantly attenuated the antioxidant effect of GIP. GIP increased glucose transporter 3 (GLUT3) expression via up-regulating the level of hypoxia-inducible factor 1α (HIF-1α) in an Akt-dependent manner.
GIP increases GLUT3 expression and promotes glucose intake in neurons, which exerts an antioxidant effect and protects neuronal cells from oxidative stress both in vitro and in vivo.
葡萄糖依赖性胰岛素释放肽（GIP）是葡萄糖依赖性胰岛素释放肽受体（GIPR）的配体，在消化系统中发挥重要作用。近年来，GIP 被视为一种调节局部代谢环境的激素样肽。在这项研究中，我们研究了 GIP 对神经元的抗氧化作用，并探讨了可能的机制。
使用细胞计数试剂盒-8（CCK-8）测量细胞存活率。TdT 介导的 dUTP 缺口末端标记（TUNEL）用于体外和体内检测细胞凋亡。使用 2'，7'-二氯二氢荧光素二乙酸酯（DCFH-DA）探测活性氧（ROS）水平，并用 2-NBDG 检测葡萄糖摄取。免疫荧光染色和 Western blot 用于评估细胞和组织中的蛋白水平。苏木精-伊红（HE）染色、免疫荧光染色和示踪用于观察损伤脊髓的形态。巴索-比蒂-布雷森汉（BBB）测定用于评估脊髓损伤后的功能恢复。
GIP 降低了培养神经元和损伤脊髓中 ROS 水平并保护细胞免于凋亡。GIP 促进了损伤脊髓的伤口愈合和功能恢复。GIP 显著增加了培养神经元的葡萄糖摄取。同时，葡萄糖摄取的抑制显著减弱了 GIP 的抗氧化作用。GIP 通过以 Akt 依赖性方式上调缺氧诱导因子 1α（HIF-1α）的水平来增加葡萄糖转运蛋白 3（GLUT3）的表达。
GIP 增加了神经元中 GLUT3 的表达并促进了葡萄糖摄取，从而在体外和体内发挥抗氧化作用并保护神经元细胞免受氧化应激。
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