Glucagon-like peptide 1 improves insulin resistance in vitro through anti-inflammation of macrophages

• Published in: Brazilian journal of medical and biological research 2016-01, Vol.49 (12), p.e5826-e5826
• Main Authors: Guo, C, Huang, T, Chen, A, Chen, X, Wang, L, Shen, F, Gu, X
• Format: Article
• Language: English
• Subjects: Adipose inflammation; Adipose Tissue - metabolism; Animals; BIOLOGY; Biomedical Sciences; Care and treatment; Cell Migration Assays; Diabetes; Glucagon; Glucagon-like peptide; Glucagon-Like Peptide 1 - pharmacology; Humans; Inflammation - drug therapy; Inflammation - metabolism; Inflammation Mediators - pharmacology; Insulin Resistance; Macrophage infiltration; Macrophages; Macrophages - drug effects; Macrophages - metabolism; MEDICINE, RESEARCH & EXPERIMENTAL; Mice; Peptides - pharmacology; Type 2 diabetes; Venoms - pharmacology
• ISSN: 0100-879X; 1414-431X; 1414-431X
• DOI: 10.1590/1414-431X20165826

Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the inflammatory response of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also inhibited the macrophage secretion of inflammatory cytokines including TNF-β, IL-6, and IL-1β. Furthermore, we observed that lipopolysaccharide (LPS)-induced macrophage conditioned media could impair insulin-stimulated glucose uptake. This effect was compensated by treatment with the conditioned media from macrophages treated with the combination of LPS and exendin-4. It was also observed that exendin-4 directly inhibited the activation of NF-κB in macrophages. In conclusion, our results indicated that GLP-1 improved inflammatory macrophage-derived insulin resistance by inhibiting NF-κB pathway and secretion of inflammatory cytokines in macrophages. Furthermore, our observations suggested that the anti-inflammatory effect of GLP-1 on macrophages can contribute to GLP-1 analogue therapy of T2D.