胰腺中胰岛β-细胞分泌的胰岛素是调节机体糖代谢最重要的激素。在营养缺乏条件下细胞内过多的胰岛素的分选调控机制目前还不十分清楚。我们前期研究结果发现糖尿病大鼠胰腺中Rab26的mRNA水平显著升高，过表达Rab26导致β-细胞分泌到细胞外的胰岛素减少，Western-blot检测发现过表达Rab26促进Proinsulin降解，进一步研究发现Rab26可结合到胰岛素分泌小体以及自噬体，并且促进细胞自噬发生，因此，我们推测Rab26可能调控胰岛素分泌小体与自噬体互作,并走向自噬降解途径，从而调控胰岛素分泌。本课题将围绕Rab26深入研究Rab26对胰岛素分泌的调控作用，胰岛素分泌小体与自噬体之间的互作关系，深入研究Rab26相互作用的分子网络，揭示其调控胰岛素分泌及相关生理功能的新机制。

Insulin secreted from β-cell is the most important hormone to maintain the glucose homeostasis. Under nutrient depletion, cells will decrease secretion and enhance degradation of insulin, however, the mechanisms remain unclear. Our primary studies revealed that Rab26 mRNA increase significantly in diabetes rat, over-expressing Rab26 inhibits insulin secretion in β-cells, Western-blot experiments demonstrated that Rab26 promotes proinsulin degradation, further examination showed Rab26 can associate with both insulin granule and autophagosome ,and enhance autophagy, suggesting that Rab26 may mediate the interaction of insulin granule with autophagosome and regulate insulin granule autophagic degradation. In this project, we will focus on Rab26 to investigate how Rab26 regulates insulin secretion and the interaction of insulin granule with autophagosome, and the molecular interaction network to uncover novel mechanism for insulin secretion and the related physiological functions.