Glucagon-like Peptide Receptor Agonists Attenuate Advanced Glycation End Products-Induced Inflammation in Rat Mesangial Cells

Jui-Ting Chang, Yao-Jen Liang, Chia-Yu Hsu, Chao-Yi Chen, Po-Jung Chen, Yi-Feng Yang, Yen-Lin Chen, Dee Pei, Jin-Biou Chang, Jyh-Gang Leu

BMC Pharmacol Toxicol. 2017 Oct 24;18(1):67.

PMID: 29065926

Abstract:

Background:




Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production play major roles in progression of diabetic nephropathy. Anti-RAGE effect of peroxisome proliferator-activated receptor-delta (PPARδ) agonists was shown in previous studies. PPARδ agonists also stimulate glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells.













Methods:




In this study, the individual and synergic anti-inflammatory effects of GLP-1 receptor (exendin-4) and PPARδ (L-165,041) agonists in AGE-treated rat mesangial cells (RMC) were investigated.













Results:




The results showed both exendin-4 and L-165,041 significantly attenuated AGE-induced IL-6 and TNF-α production, RAGE expression, and cell death in RMC. Similar anti-inflammatory potency was seen between 0.3 nM exendin-4 and 1 μM L-165,041. Synergic effect of exendin-4 and L-165,041 was shown in inhibiting cytokines production, but not in inhibiting RAGE expression or cell death.













Conclusions:




These results suggest that both GLP-1 receptor and PPARδ agonists have anti-inflammatory effect on AGE-treated rat mesangial cells.

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