类固醇性糖尿病是糖皮质激素临床应用中常见的副作用，胰岛β细胞凋亡是其重要原因，但确切分子机制尚不清楚。我们前期建立了糖皮质激素诱导β细胞凋亡的细胞模型，通过基因芯片差异、基因沉默实验首次发现E4BP4参与了糖皮质激素直接诱导的β细胞凋亡。随后动物实验发现糖皮质激素除了直接引起β细胞凋亡外，其引起的动物血糖血脂升高是引起β细胞凋亡的另一重要因素，而糖脂毒性同样也能显著诱导β细胞E4BP4的表达。据此我们推测E4BP4可能介导了糖皮质激素直接诱导的β细胞凋亡以及糖皮质激素通过糖脂毒性间接诱导的β细胞凋亡，在类固醇性糖尿病发病过程中发挥重要作用。本研究拟应用已建立的稳定敲降或可诱导表达E4BP4的β细胞系、类固醇性糖尿病动物模型、β细胞特异性E4BP4敲除小鼠，阐明E4BP4介导糖皮质激素诱导胰岛β细胞凋亡的分子机制，并筛选保护药物，为阐明类固醇性糖尿病的发病机制和药物防治提供实验依据。

Steroid diabetes is the most frequent side effect of glucocorticoid treatment. The apoptosis of pancreatic β cells is the main reason, but the underlying molecular mechanisms remain to be elucidated. In our previous work, we established in vitro cell model to mimic the pancreatic β cell apoptosis under glucocorticoid treatment. Genes that related to glucocorticoid-induced β cell apoptosis were screened by microarray, and the candidate gene E4BP4 was first confirmed to have an important role in glucocorticoid-induced β cell apoptosis by E4BP4 knockdown experiment. Further in vivo studies in mice showed that elevated blood glucose and serum lipid evoked by glucocorticoid may be another important factors that can lead to β cell apoptosis. In addition, glucolipotoxicity also can significantly increased the expression of E4BP4. Based on these results, we speculate that E4BP4 not only mediates glucocorticoid directly induced β cell apoptosis，but also mediates glucolipotoxicity induced β cell apoptosis. In this study, we want to investigate the role of E4BP4 in glucocorticoid-induced β cell apoptosis by using established E4BP4 stable knockdown MIN6 cells, E4BP4 inducible MIN6 cells, dexamethasone-induced diabetic mice model, β cell specific E4BP4 knockout mice, and elucidate its molecular mechanism. This study will provide new experimental data for unraveling the underlying mechanisms of steroid diabetes.