The role of immune receptor NOD1 in insulin resistance of human adipocytes
10.3760/cma.j.issn.1000-6699.2013.05.017
- VernacularTitle:免疫受体NOD1在人脂肪细胞胰岛素抵抗形成中的作用
- Author:
Yijun ZHOU
;
Yuling SONG
;
Ai LI
;
Yan LI
;
Hui ZHOU
- Publication Type:Journal Article
- Keywords:
Nucleotide-binding oligomerization domain-containing protein 1;
Insulin resistance;
Human adipocytes;
γ-D-Glu-meso-diaminopimelic acid;
Inflammation
- From:
Chinese Journal of Endocrinology and Metabolism
2013;(5):417-421
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in inducing insulin resistance in differentiated human adipocytes.Methods Human preadipocytes obtained via liposuction were induced to differentiate into mature adipocytes.iE-DAP,a specific ligand for NOD1,was administered to human adipocytes in culture.NF-κB transcriptional activity and proinflammatory cytokines production were determined by luciferase assay and enzyme-linked immunosorbent assay.Glucose uptake in adipocytes was measured by 2-deoxy-D-[3 H] glucose uptake (P＜0.05).The expression of phosphatidylinositol-3-kinase p85 (PI-3K p85),insulin receptor substrate-1 (IRS-1) and Akt phosphorylations were detected by Western blotting.Results NF-κB transcriptional activity and cytokines such as interleukin (IL)-6,IL-8,and monocyte chemotactic protein 1 secretion were markedly increased after stimulation with iE-DAP (P＜0.05 or P＜0.01).Insulin-induced glucose uptake was decreased with the activation of NOD1 in a dose-and time-dependent fashion.NOD1 activation weakened insulin signal transduction as being revealed by increasing IRS-1 Ser307phosphorylation,reducing protein expression of PI-3K p85,and attenuating insulin-induced phosphorylation of Akt on Ser473 and Thr308in human adipocytes.Conclusion These results indicate that NOD1 activation induces inflammatory response and insulin resistance via IRS-1/PI3-K/Akt signaling pathway in human adipocytes.
