Glucagon-like peptide receptor agonists attenuate advanced glycation end products-induced inflammation in rat mesangial cells.

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.

• Authors: 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
• Journal: BMC pharmacology & toxicology (BMC Pharmacol Toxicol) Vol. 18 Issue 1 Pg. 67 (10 24 2017) ISSN: 2050-6511 [Electronic] England
• PMID: 29065926 (Publication Type: Journal Article)

Chemical References

• 4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid
• Anti-Inflammatory Agents
• Antioxidants
• Glucagon-Like Peptide-1 Receptor
• Glycation End Products, Advanced
• Interleukin-6
• PPAR delta
• Peptides
• Phenoxyacetates
• Tumor Necrosis Factor-alpha
• Venoms
• Exenatide

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Cell Survival (drug effects)
• Cells, Cultured
• Exenatide
• Glucagon-Like Peptide-1 Receptor (agonists)
• Glycation End Products, Advanced
• Inflammation (chemically induced, metabolism)
• Interleukin-6 (metabolism)
• Mesangial Cells (drug effects, metabolism)
• PPAR delta (agonists)
• Peptides (pharmacology)
• Phenoxyacetates (pharmacology)
• Rats
• Tumor Necrosis Factor-alpha (metabolism)
• Venoms (pharmacology)