Vaspin在胰岛β细胞炎症、胰岛素抵抗及氧化应激中的作用及机制研究

The islet β-cells play an important role in the pathogenesis of type 2 diabetes. Free fatty acids have been shown to cause inflammation and insulin resistance of islet cells, and induce oxidative stress in β-cells by increasing the level of reactive oxygen species (ROS), which in turn impair islet β-cells, resulting in decreased synthesis and secretion of insulin. Vaspin, an adipocytokine, possesses insulin-sensitizatiing, anti-inflammatory and anti-oxidative stress effects. On the basis of our previous works, this study, by utilizing western blot, RT-PCR, flow cytometry, islet cell surface perfusion and high normal glucose insulin clamps test, will further examine the influence of Vaspin on inflammatory signaling pathways, insulin receptor signaling pathways and oxidative stress response pathways in islet β-cells at the cellular and animal levels, and ultimately determine whether Vaspin can inhibit inflammation, improve the insulin resistance and suppress oxidative stress of islet cells, and whether Vaspin can protect islet cells and improve the function of islet cells. Accomplishments of this project will allow us to have a better understanding of the role and mechanism of Vaspin on insulin resistance, oxidative stress and inflammatory response of the pancreatic islet β-cells, and provide a practical and valuable basis for the treatment and prevention of Vaspin in type 2 diabetes.

胰岛β细胞的功能在2型糖尿病的发病机制中发挥重要的作用。游离脂肪酸可引起胰岛炎症反应及胰岛细胞的胰岛素抵抗，还可通过增加反应性氧化物的浓度导致胰岛细胞的氧化应激，进而损伤β细胞，降低其功能而影响胰岛素的合成和分泌。脂肪细胞因子Vaspin具有胰岛素增敏、抗炎以及抗氧化应激的效应。在我们前期的工作基础上，本课题将通过western blot、RT-PCR、流式细胞术、胰岛细胞表面灌注、正常葡萄糖高胰岛素钳夹试验等技术，在细胞和动物水平检测Vaspin对β细胞炎症、胰岛素受体及氧化应激信号通路的影响，从而探讨Vaspin是否具有抑制β细胞的炎症、改善β细胞的胰岛素抵抗以及抗氧化应激的作用，进而保护胰岛细胞，改善其功能。本研究项目的完成，将使我们对Vaspin在β细胞的胰岛素抵抗、氧化应激及炎症中的作用及机制有新的认识和理解，并为Vaspin对2型糖尿病的治疗和预防提供有价值的实验依据。

胰岛β细胞衰退和功能障碍在2型糖尿病发展过程中起重要作用。游离脂肪酸可引起胰岛的炎症反应、胰岛素抵抗及氧化应激，损伤β细胞，影响胰岛素的合成与分泌。脂肪细胞因子Vaspin具有胰岛素增敏、抗炎及抗氧化应激的效应，然而其具体机制尚不清楚。本项目通过一系列细胞和动物实验证实Vaspin可以改善高脂喂养大鼠的胰岛分泌功能，其具体机制是通过抑制IκBα/NF-κB信号通路，促进PI3K/Akt、Nrf2/ ARE信号通路转导，进而改善胰岛β细胞分泌功能，促进胰岛β细胞增殖，减少细胞凋亡。此外，Vaspin也可通过IκBα/NF-κB、PI3K/Akt信号通路改善胰岛素抵抗大鼠外周靶组织的炎症状态及胰岛素抵抗程度。本研究项目的完成，使我们对Vaspin的作用机制有了更深一步的认识和理解，为2型糖尿病的治疗和预防提供新的治疗策略。