Liraglutide inhibits the apoptosis of human nucleus pulposus cells induced by high glucose through PI3K/Akt/caspase-3 signaling pathway.
Ming-Yan Y1, Jing Z2, Shu-Qin G1, Xiao-Liang B1, Zhi-Hong L3, Xue Z1.
Author information
1Department of Endocrinology, Baoding NO.1 Central Hospital, 320 Changcheng North Street, Lianchi District, Baoding City, Hebei Province, China.2Department of Cardiology, Affiliated Hospital of Hebei University, Baoding City, Hebei Province, China.3Department of Endocrinology, Baoding NO.1 Central Hospital, 320 Changcheng North Street, Lianchi District, Baoding City, Hebei Province, China lizhihongmd@163.com.
Abstract
Diabetes mellitus (DM) is a potential etiology of disc degeneration. Glucagon-like peptide-1 (GLP-1) is currently regarded as a powerful treatment option for type 2 diabetes. Apart from the beneficial effects on glycaemic control, GLP-1 has been reported to exert functions in a variety of tissues on modulation of cell proliferation, differentiation, and apoptosis. However, little is known regarding the effects of GLP-1 on nucleus pulposus cells (NPCs). In the present study, we investigated the effects of liraglutide (LIR), a long-lasting GLP-1 analogue, on apoptosis of human NPCs and the underlying mechanisms involved. We confirmed the presence of GLP-1 receptor (GLP-1R) in NPCs. Our data demonstrated that liraglutide inhibited the apoptosis of NPCs induced by high glucose (HG), as detected by Annexin V/Propidium Iodide (PI) and ELISA assays. Moreover, liraglutide down-regulated caspase-3 activity at intermediate concentration (100 nM) for maximum effect. Further analysis suggested that liraglutide suppressed reactive oxygen species (ROS) generation and stimulated the phosphorylation of Akt under HG condition. Pretreatment of cells with the Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (LY) and small interfering RNAs (siRNAs) GLP-1R abrogated the liraglutide-induced activation of Akt and the protective effects on NPCs’ apoptosis. In conclusion, liraglutide could directly protect NPCs against HG-induced apoptosis by inhibiting oxidative stress and activate the PI3K/Akt/caspase-3 signaling pathway via GLP-1R.
© 2019 The Author(s).
KEYWORDS:
apoptosis; liraglutide; nucleus pulposus cells; oxidative stress; signaling pathway