丝氨酸合成回补代谢通路在TSA保护胰岛功能中的作用研究

细胞代谢调节领域的研究进展预示着蛋白乙酰化介导的代谢重编程在强化特定细胞功能及疾病治疗中的巨大应用前景，而如何维持胰岛功能是防治2型糖尿病的关键问题。预实验发现去乙酰化酶抑制剂曲古抑菌素A（TSA）能显著增加胰岛?细胞分泌能力，保护胰岛功能，伴随丝氨酸合成回补代谢通路相关基因显著上调，据此我们提出假设：TSA介导的蛋白乙酰化可以通过激活胰岛细胞的回补代谢通路，增加胰岛素分泌扩大途径代谢性信号分子的产生和胰岛素分泌能力，保护胰岛功能。本研究将系统观察TSA对胰岛β细胞丝氨酸合成回补代谢通路的影响及其在胰岛素分泌和胰岛功能保护中的可能作用，探索乙酰化调节胰岛代谢和功能的新机制，最终为深入了解2型糖尿病的发病机制及寻找针对胰岛β细胞保护作用的药物提供理论基础和研发思路。

Protein acetylation-induced metabolic reprogramming has become an important research topic for enhancing specific cell function and disease therapy, and the preservation of pancreatic β-cell function is a major point of research in preventing and treating type 2 diabetes. Our previous data show that protein acetylation induced by trichostatin A (TSA) increases glucose-stimulated insulin secretion from isolated rat islets, along with increased gene expressions in serine biosynthesis pathway. So we propose the research hypothesis：protein acetylation may increase insulin secretion from pancreatic β-cell by stimulating serine biosynthesis pathway, increasing the production of metabolic signaling molecular in amplification pathway of insulin secretion, and thus protect pancreatic β-cell function. We will observe the effect of protein acetylation on serine biosynthesis activity and insulin secretion, and explore the mechanism involved. These will widen the knowledge of protein acetylation-induced metabolic regulation and insulin secretion and provide possible therapeutic target for β-cell protection.