| Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 101 === Diabetic nephropathy is the leading cause of end stage renal disease which needs regular dialysis therapy. Advanced glycation end products (AGE) and receptors of AGE (RAGE) play important pathological roles in progression of diabetic nephropathy. Both glucagon-like peptide-1 (GLP-1) and peroxisome proliferator-activated receptors (PPARs) have been reported to reduce AGE or RAGE-induced inflammatory reaction and cell apoptosis. In this study, the mechanism about inhibition of GLP-1 and PPARδ was studied using rat mesangial cells.
Incubation of AGE and PPARδ agonists increased GLP-1 receptor expression (mRNA and protein) in rat mesangial cells. Coadministration of AGE and PPARδ agonist showed synergic effects in GLP-1 receptor expression. Regarding to GLP-1 agonist, exendin, this study revealed both PPARδ agonist and GLP-1 agonist exendin could suppress RAGE mRNA and protein expressions induced by AGE with synergic effect. In the meantime, both coadministration of PPARδ agonist and GLP-1 agonist exendin could improve cell survival as well as inflammatory cytokines suppression.
In conclusion, PPARδ agonist and GLP-1 agonist could decrease AGE induced RAGE mRNA and protein expression, and improve cell survival condition. These findings may provide important implications for the understanding of the interactions of AGE, RAGE, GLP-1, and PPARδ, and development of potential therapeutic interventions for diabetic nephropathy.
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