title: Exendin-4 Promotes Survival of Mouse Pancreaticβ-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway.
abstract: Type 2 diabetes is a heterogeneous disorder that develops as a result of relatively inappropriate insulin secretion and insulin resistance. Increased levels of free fatty acids (FFAs) are one of the important factors for the pathogenesis of type 2 diabetes and contribute to defectiveβ-cell proliferation and increasedβ-cell apoptosis. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to possess an antiapoptotic effect, by increasingβ-cell mass and improvingβ-cell function. However, their effects onβ-cells in vitro against lipotoxicity have not been elucidated completely. In this study, we investigated whether the GLP-1 receptor agonist exendin-4 displays prosurvival effects in pancreaticβ-cells exposed to chronic elevated FFAs. Results showed that exendin-4 inhibited apoptosis induced by palmitate in MIN6 cells. After 24 h of incubation, exendin-4 caused rapid activation of extracellular signal-related kinase 1/2 (ERK1/2) under lipotoxic conditions. The ERK1/2 inhibitor PD98059 blocked the antilipotoxic effect of exendin-4 on MIN6 cells. Exendin-4 also inhibited the mitochondrial pathway of apoptosis. This inhibition is associated with upregulation of BCL-2. Our findings suggested that exendin-4 may exert cytoprotective effects through activation of ERK1/2 and inhibition of the mitochondrial apoptosis pathway.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, China.
authors.forename: Jianqiu
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, China.
authors.forename: Hongzhi
authors.identifier: 0000-0003-3874-450X
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, China.
authors.forename: Difei
authors.identifier: 0000-0003-1525-5631
authors.initials: D
authors.lastname: Wang