Figure 9. Schematic diagram in STZ-induced diabetic nephropathy showing GLP-1/Ex-4 increases detoxification of methylglyoxal (MGO) through the regulation of glyoxalase-1. Hyperglycemia-induced MGO accumulation under diabetic condition activates the AGEs-RAGE signaling pathway, which results in diabetic nephropathy through upregulation of the expression of inflammatory cytokines and fibrotic factors. In contrast, GLP-1/Ex-4 enhances detoxification of MGO, producing D-lactate through the regulation of glyoxalase-1 expression. GLP-1: Glucagon like peptide-1, Ex-4: Exendin-4, Nrf-2: Nuclear factor-erythroid 2 p45 subunit-related factor-2, AGEs: Advanced glycation end products, RAGE: Receptor AGE.