糖毒性损坏胰岛β细胞功能及其所致的胰岛素分泌降低是2型糖尿病发生发展的重要环节。然而糖毒性抑制β细胞功能的机理迄今仍不清楚。作为细胞骨架成分，微丝在β细胞胞膜下形成网状结构，微丝的解聚是胰岛素囊泡出胞的前提。我们的前期工作发现糖毒性导致β细胞内微丝聚集，形成长且稳固的应力纤维；在该条件下葡萄糖失去解聚微丝的能力，也失去刺激胰岛素分泌的能力。GLP-1处理糖毒性β细胞导致应力纤维解聚，恢复葡萄糖刺激的胰岛素分泌。以此为基础，我们将采用分子生物学、电生理和免疫细胞化学等方法探讨①糖毒性是否通过Rho A-ROCK/Formins促进应力纤维的形成；②应力纤维是否通过干扰囊泡的出胞机制抑制胰岛素分泌；③GLP-1是否通过激活ERK1/2导致应力纤维解聚并恢复葡萄糖刺激的胰岛素分泌。研究结果将为揭示糖毒性抑制β细胞功能的机理提供新理论，也将为阐明GLP-1改善糖毒性β细胞功能提供新的科学依据。

It has been revealed that glucotoxicity inhibits insulin secretion via blunting pancreatic β-cell functions, which exacerbates type 2 diabetes. However, the mechanisms underlying remain largely unknown. As a cytoskeleton, F-actin is organized as a web beneath the plasma membrane. It is widely accepted that F-actin remodeling is essential for insulin release from pancreatic β-cells. Our data show that β-cells at glucotoxicity have abundant stress fibers, accompanied by loss of glucose-induced F-actin depolymerization and insulin secretion. Treatment with GLP-1 resulted in F-actin depolymerization and restored glucose-stimulated insulin secretion. By employing molecular biological, electrophyisological and immunocytochemistry approaches, we would therefore explore whether ① Rho A-ROCK/Formins would be involved in glucotoxicity-increased stress fibers in β-cells;② stress fibers would impede priming and exocytosis of insulin containing granules;③ GLP-1 would induced F-actin depolymerization via activation of ERK1/2 in β-cells at glucotoxicity. The results will shed light on revealing the cellular mechanisms underlying glucotoxicity-suppressed β-cell functions, as well as the protective effects of GLP-1 against glucotoxicity.