Glucagon-like peptide-1 receptor mediates the improvement in glycolipid metabolism disorder via AKT and AMPK signalling pathways in L02 cells with insulin resistance

Abstract

Glucagon-like peptide 1 (GLP-1) has previously been found to regulate glycolipid metabolism in the liver by promoting insulin secretion. However, the presence of GLP-1 receptors (GLP-1R) in the human liver has not been determined. In this research, GLP-1R was found to be expressed in L02 cells and decreased in insulin resistant (IR) cells. Compared with LG treatment group, GLP-1R knockdown significantly decreased glucose utilization (from 143.13% to 118.41%.) and intracellular glycogen content (from 122.77% to 105.72%). Furthermore, the transcription levels of PEPCK and G6Pase increased, and the phosphorylation levels of AKT, FOXO1 and GSK3β decreased in siGLP-1R group. Similarly, the contents of triglyceride and total cholesterol in siGLP-1R group increased by 43.23% and 24.19%, respectively. PCR and WB results showed that knockdown of GLP-1R increased the levels of ACC, FAS, and SREBP-1c, and decreased the levels of CPT-1 via AMPK pathway. GLP-1R knockdown changed the LG-induced promotion of glucose utilization and inhibition of lipid synthesis. These findings demonstrated that GLP-1R is the molecular basis for GLP-1 to improve glycolipid metabolism in L02 cells.