胰岛β细胞凋亡在糖尿病的发生、发展中发挥重要作用。丝裂原活化的蛋白激酶（MAPK）通路可能参与了致炎性细胞因子及氧化应激所致的胰岛β细胞凋亡，并在胰高糖素样肽1（GLP-1）保护胰岛β细胞凋亡中发挥重要作用，但具体机制尚不明确。课题组前期的研究发现：ERK1/2 MAPK在胰岛β细胞葡萄糖刺激下的胰岛素分泌（GSIS）中发挥重要作用；致炎性细胞因子IL-1β可通过抑制ERK1/2活化损伤β细胞GSIS；GLP-1受体激动剂可通过恢复ERK1/2的活化保护IL-1β所致的胰岛β细胞损伤。本项目在此基础上拟开展以下研究：探讨致炎性细胞因子，氧化应激对胰岛β细胞MAPK信号转导系统的影响、不同MAPK信号通路之间的调控机制以及阐明GLP-1通过调控MAPK信号系统发挥抗凋亡作用的分子机制。本研究有助于进一步阐明胰岛β细胞的凋亡机制，为糖尿病的防治提供新的干预靶点。

Islet β cell apoptosis plays a critical role in the pathogenesis of diabetes mellitus. Although MAP kinase signal transduction pathway may participate in islet β cell apoptosis induced by various damage factors, such as inflammatory cytokines and oxidative stress and associate with protective role of glucagon like peptide-1 (GLP-1), the exact mechanism remains to be elucidated. Our previous work shows that ERK1/2 MAPK signal transduction pathway may have an important effect on glucose stimulated insulin secretion (GSIS) in β cells; pro-inflammatory cytokine IL-1β can impair GSIS in islet β cells by inhibiting ERK1/2 signal transduction pathway activation; GLP-1 receptor agonist can protect IL-1β induced islet β cell damage by restoring ERK1/2 activation. In the present study, we will elucidate the effect of pro-inflammatory cytokines and oxidative stress on various MAPK signal transduction pathway (ERK，p38，JNK pathway) and their cross interaction, investigate the molecular mechanism of GLP-1 against islet β cell apoptosis by manipulating MAPK signal transduction pathway . This study may be beneficial to further define the mechanism of β-cell apoptosis and find new therapeutic targets for diabetes mellitus prevention and management.