Effect of glucagon-like peptide 1 on autophagy mediated by AMP activated protein kinase-mammalian target of rapamycin pathway in type 2 diabetic rats with Alzheimer′s disease

Objective To explore the effect of glucagon-like peptide 1 (GLP-1) on autophagy mediated by AMP activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) pathway in type 2 diabetic rats combined with Alzheimer′s disease (AD). Method Total 80 SD rats were prepared as type 2 diabetes mellitus (T2DM) combined with AD models and 20 SD rats were as controls. Models were divided into model group, GLP-1 group (Liraglutide), GLP-1+AMPK inhibitor group (Compound C) and GLP-1+mTOR agonist group (L-leucine). After 1 week, bilateral hippocampus were extracted and Tau protein was detected by immunohistochemistry, p-AMPK/AMPK, p-mTOR/mTOR, LC3Ⅱ/LC3Ⅰ and beclin-1 were detected by western blotting. Result Levels of Thep-mTOR/mTOR expression in the control group, model group, GLP-1 group, GLP-1+AMPK inhibitor group, GLP-1+mTOR agonist group were 0.19±0.03, 0.37±0.04, 0.23±0.02, 0.39±0.04 and 0.38±0.04, respectively; For Thep-mTOR/mTOR expression, levels in the model group were higher than those in the control group, levels in the GLP-1 group were lower than those in the model group, and levels in the GLP-1+AMPK inhibitor group and GLP-1+mTOR agonist group were higher than those in the GLP-1 group. The differences were significant between groups (t=2.739-2.936, P<0.05). Levels of p-AMPK/AMPK expression in the control group, model group, GLP-1 group, GLP-1+AMPK inhibitor group, GLP-1+mTOR agonist group were 0.89±0.10, 0.25±0.04, 0.90±0.11, 0.60±0.06 and 0.64±0.05 respectively; Levels of LC3Ⅱ/LC3Ⅰ expression were 2.29±0.30, 0.44±0.06, 1.85±0.20, 1.45±0.15 and 1.44±0.14 respectively; Levels of beclin-1 expression were 0.60±0.08, 0.28±0.03, 0.43±0.04, 0.34±0.04 and 0.33±0.02 respectively; For p-AMPK/AMPK, LC3Ⅱ/LC3Ⅰ, beclin-1 expression, levels in the model group were lower than those in the control group, levels in the GLP-1 group were higher than those in the model group, and levels in the GLP-1+AMPK inhibitor group and GLP-1+mTOR agonist group were lower than those in the GLP-1 group. The differences were significant between groups (t=3.062-11.980, all P<0.05). Conclusion GLP-1 could activate the autophagy response in T2DM combined with AD rats via AMPK-mTOR signaling pathway. Key words: Diabetes mellitus, type 2; Alzheimer′s Disease; Glucagon-like peptide 1; Autophagy; Adenosine monophosphate activated protein kinase