Liraglutide inhibits the apoptosis of human nucleus pulposus cells induced by high glucose through PI3K/Akt/caspase-3 signaling pathway

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.

Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Cancer Progression via Activating PI3K/AKT/mTOR Pathway

“…Some studies have confirmed that inhibition of the PI3K/Akt/mTOR pathway is of great significance for CRC treatment [ 26 , 27 ]. The PI3K/Akt pathway can inhibit CRC cell apoptosis through its effects on caspase, Bcl, FOXO, and mTOR genes [ 23 , 28 ]. mTOR activation, in particular, mediates downstream molecules of the PI3K/Akt/mTOR signaling pathway, subsequently affecting cell growth, apoptosis, and metabolism [ 29 , 30 ].…”

The Impact of Glucagon-Like Peptide 1 Receptor Agonists on Bone Metabolism and Its Possible Mechanisms in Osteoporosis Treatment

“…The PI3K/AKT signaling pathway plays an important role in regulating proliferation, osteoblast differentiation and osteoclast differentiation, apoptosis ( Zhang et al, 2020 ; Ye et al, 2019 ). Studies have shown that GLP-1RA can regulate PI3K/AKT signaling pathway through GLP-1R to alleviate cell apoptosis ( Xie et al, 2018 ; Ming-Yan et al, 2019 ). In addition, liraglutide could increase intracellular cAMP level and phosphorylation of AKT and the inhibitors LY294002, and GLP-1R siRNA could partially block the liraglutide-induced signaling activation and attenuated the facilitating effect of liraglutide.…”

Long non-coding RNA-PCGEM1 contributes to prostate cancer progression by sponging microRNA miR-129-5p to enhance chromatin licensing and DNA replication factor 1 expression

“…LNCaP and 22RV1 cells (1 × 10 5 ) were lysed in cell lysis buffer for 15 min at 4°C, and protein concentration was determined using Pierce bicinchoninic acid (BCA) (Thermo Scientific). After incubating the reaction mixture system composed of cell lysate (10 μL), detection buffer solution (80 μL), and Ac-DEVD-pNA (10 μL, 2 mM) in 96-well plates at 37°C for 2 h, the optical density was measured using a microplate reader at 405 nm [ 23 ].…”