PK2调节血糖平衡的分子机制研究

血糖平衡是机体最为重要的稳态平衡，当这种平衡失调时，可导致人体出现以糖尿病为代表的多种疾病症状，因此，找到血糖调节相关基因并研究其调节机制是目前治疗2型糖尿病的新方向。前动力蛋白PK2是一种小分子分泌蛋白，与其受体PKR1/2形成的信号转导系统在生物体内调控了一系列生物学功能，包括血管生成、生物节律、神经干细胞迁移、疼痛、情绪反应以及摄食等，但其在调节血糖平衡方面的作用未见有报道。我们在前期的研究中发现PK2是一个潜在的血糖调节因子，本课题拟研究PK2具体血糖平衡调节机制，推测其可能是通过与其受体（PKR1/2）结合引起下游信号传递变化从而调节胰岛素的分泌来完成的，因此，拮抗PK2 的信号传递可能是一个新型糖尿病药物开发的靶位点；由此，我们拟进一步研究新开发的PK2 受体小分子拮抗剂对糖尿病的可能治疗作用，为开发新的2型糖尿病治疗药物提供理论依据和研究基础。

Glucose homeostasis is the most important steady equilibrium in the body. Impaired glucose homeostasis may lead to many diseases or syndromes represented by diabetics. Therefore, a new direction for developing medical treatments that address type 2 diabetics have focused on how to identify the genes related to the regulation of blood glucose and study the regulatory mechanism in it. Prokineticin-2, a small molecular secretory protein, complexes with its receptor PKR1/2 to form a signal transduction system that regulates a series of biological functions inside the organism, including angiogenesis, biological rhythm, immigration of neural stem cells, pains, emotional reactions, ingestion, etc. However, its role in regulating glucose homeostasis has not yet been reported. It was found in preliminary studies that PK2 is a potential blood glucose regulator. This research project proposes to study the specific mechanism by which PK2 regulates glucose homeostasis, presumably accomplished by binding to its receptor PKR1/2 to give rise to changes in downstream signal transmission to regulate the secretion of insulin. Thus, the signal transduction that antagonizes PK2 possibly provides a new target for developing new diabetes medicines. For this regard, we propose to further study the potential therapeutic effect of the newly developed small molecular PK2 receptor antagonist on diabetics, thus providing theoretical and research bases for developing new diabetes drugs for treatment of type 2 diabetics.