脂毒性凋亡是造成胰岛β细胞功能衰竭的重要机制之一，寻找有效的治疗靶点抗脂毒性凋亡从而防治β细胞功能衰竭是目前糖尿病的研究热点。我们新近发现激活过氧化物酶体增值物活化受体（PPAR）家族中的亚型PPARβ/δ可抗β细胞脂毒性凋亡，前期实验已经证实这种机制可通过上调GLP-1R介导。游离脂肪酸受体1（GPR40）可结合中长链饱和或不饱和脂肪酸，具有抗胰岛β细胞脂毒性凋亡的作用，但其确切机制尚不清。因此，我们拟深入探讨激活PPARβ/δ对活体胰岛功能的改善以及通过调节GPR40的表达介导β细胞抗脂毒性凋亡的机制。本项目采用自发性2型糖尿病大鼠和胰岛β细胞株INS-1E细胞建立脂毒性凋亡模型，开展相应研究，力图为抗β细胞凋亡防治2型糖尿病提供新的途径或靶点。

One of the key factors responsible for the development of type 2 diabetes is the free fatty acid-induced lipotoxic apoptosis of β cells. Looking for an effective therapeutic target which prevents β cells from lipotoxic apoptosis is a hotspot of diabetic investigation nowadays. We previously found that activated peroxisome proliferator-activated receptor (PPAR)β/δ can protect pancreatic β cells against lipotoxic apoptosis. Our previous experiments have confirmed that this mechanism can be mediated by raising expression of GLP-1R. FFA receptor (GPR40) can combine with long-chain saturated or unsaturated fatty acid, and make the role of anti-lipotoxic apoptosis. However, the underlying molecular mechanism remained unclear. Therefore, we intend to explore whether activated PPARβ/δ could improve impaired β-cell function and suppress lipotoxic apoptosis via regulation of GPR40 expression. This study adopts spontaneous developed type 2 diabetic rats (GK rat) and islet β-cell lines (INS-1E) to construct lipotoxic apoptosis model, carrying out the corresponding research. We try to provide a new approach for the prevention β-cells from lipotoxic apoptosis.