Effects of Liraglutide on Neuronal Insulin Resistance in in vitro

• Main Author: Salinee Jantrapirom
• Other Authors: Dr. Saranyapin Potikanond
• Format: Theses and Dissertations
• Language: English
• Published: เชียงใหม่ : บัณฑิตวิทยาลัย มหาวิทยาลัยเชียงใหม่ 2020
• Online Access: http://cmuir.cmu.ac.th/jspui/handle/6653943832/69400
• Institution: Chiang Mai University

Brain insulin resistance has been shown to be associated with cognitive impairment and Alzheimer’s disease (AD). Several studies have been demonstrated that AD and type 2 diabetes mellitus (T2DM) shared some risk factors including amyloidogenesis and brain insulin resistance. Liraglutide is a long-acting GLP-1 receptor agonist using in T2DM therapy. Several studies showed that liraglutide has beneficial effects on brain function including the cognitive improvement, decreased AD-like characteristics such as amyloid plaque and also has neuroprotective effects. However, the effect of liraglutide on the model of neuronal insulin resistance with AD-like characteristics has not been thoroughly investigated yet. In the present study, the model of neuronal insulin resistance with AD-like characteristics was established by using human neuroblastoma cell line (SH-SY5Y). Those cells were induced to be insulin resistance with 100 nM insulin for 2 days. The insulin resistant characteristics were indicated as an impairment of insulin signaling, including decreased phosphorylation of insulin receptor (IR) and the down-stream signaling; AKT and GSK3β. The AD-like characteristics as indicated by increased amyloid-β and Tau phosphorylation and the expression of extracellular insoluble plaques was also found in this model. Moreover, this chronic insulin resistant condition also increased cell death by increasing Bax/Bcl2 ratio. The application of 500 nM liraglutide onto the model of neuronal insulin resistance with AD-like characteristics improved neuronal insulin sensitivity and decreased AD characteristics but it could not improve cell death. These findings suggest that liraglutide is a promising therapy for AD with insulin resistant condition.