The impact of the glucagon-like peptide 1 receptor agonist liraglutide on the streptozotocin-induced diabetic mouse kidney proteome.

Abstract

In diabetes mellitus (DM), the kidneys are exposed to increased levels of hyperglycemia‐induced oxidative stress. Elevated amounts of reactive oxygen species (ROS) are believed to provoke ultrastructural changes in kidney tissue and can eventually result in DM late complications such as diabetic nephropathy. While it is reported that glucagon‐like peptide 1 receptors (GLP‐1R) are present in the kidney vasculature, the effects of GLP‐1 on the kidney proteome in DM is not well described. Thus, we set out to investigate potential effects on the proteomic level. Here the effects of GLP‐1R agonism using the GLP‐1 analogue liraglutide are studied in the kidneys of streptozotocin (STZ)‐treated mice (n = 6/group) by label‐free shotgun mass spectrometry (MS) and targeted MS. Unsupervised and supervised multivariate analyses are followed by one‐way ANOVA. Shotgun MS data of vehicle and liraglutide‐treated mouse groups are separated in the supervised multivariate analysis and separation is also achieved in the subsequent unsupervised multivariate analysis using targeted MS data. The mouse group receiving the GLP‐1R agonist liraglutide has increased protein abundances of glutathione peroxidase‐3 (GPX3) and catalase (CATA) while the abundances of neuroplastin (NPTN) and bifunctional glutamate/proline–tRNA ligase (SYEP) are decreased compared to the STZ vehicle mice. The data suggest that GLP‐1R agonism mainly influences abundances of structurally involved proteins and proteins involved in oxidative stress responses in the STZ mouse kidney. The changes could be direct effects of GLP‐1R agonism in the kidneys or indirectly caused by a systemic response to GLP‐1R activation.