线粒体动力学稳态失衡是造成β细胞功能降低和损伤并诱发糖尿病的主要机制之一。虽然线粒体动力学稳态主要依赖线粒体分裂蛋白Drp1和线粒体融合蛋白mitofusin作用的平衡，但线粒体的自噬降解也是线粒体稳态调节的一个重要机制，并且同样受Drp1的调控。阐明β细胞治疗药物是否通过干预这些过程而保护胰岛β细胞具有重要意义。我们前期研究发现中药大黄酸能够抑制β细胞损伤中Drp1的表达，并伴有Drp1下游的线粒体自噬通路成员Pink1/Parkin的活化，因此提出大黄酸可能通过抑制Drp1而促进β细胞线粒体自噬，及时清除损伤的线粒体，维持线粒体稳态平衡，从而维持其正常功能并减轻其损伤。我们将利用原代β细胞、β细胞株NIT-1、糖尿病db/db小鼠等，采用多种技术手段，从细胞、分子多方面深入探讨大黄酸是否通过Drp1-Pink1/Parkin促进β细胞线粒体自噬从而保护β细胞。

Mitochondrial dynamic imbalance is known to contribute to progressive functional impairment and injury of islet β-cells. Although mitochondrial homeostasis is mainly determined by the balanced action between mitochondrial fission (Drp1) and fusion (mitofusin) proteins through coordinate control of mitochondrial fission and fusion, mitochondrial autophagy (mitophagy) is also involved in mitochondrial homeostasis. In addition, Drp1 is known to regulate (inhibit) mitophagy. It is important to understand whether therapeutic effect of medicine is through intervention of this process to protect β-cells. We have previously demonstrated that Rhein can prevent Drp1 upregulation, accompanied by activation of downstream molecules of Drp1, Pink1/Parkin, which is critical for mitophagy. Therefore, we propose that Rhein may promote β-cells mitophagy by preventing Drp1 upregulation and thus activating Pnk1/Parkin, thereby removing damaged mitochondria timely and protecting the cells from damage. We will utilize primary islet β cell, NIT-1 cell line, and diabetic db/db mice, and perform a variety of cellular and molecular experiments to test this hypothesis.