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

Abstract Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidenceindicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause ofinsulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the in flammatoryresponse of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not onlyattenuated macrophage infiltration, but also inhibited the macrophage secretion of in flammatory cytokines including TNF- b, IL-6, andIL-1b. 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 thecombination of LPS and exendin-4. It was also observed that exendin-4 directly inhibited the activation of NF- kB in macrophages. Inconclusion, our results indicated that GLP-1 improved in flammatory macrophage-derived insulin resistance by inhibiting NF- kBpathway and secretion of in flammatory 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.Key words: Diabetes; Glucagon-like peptide; Macrophage infiltration; Adipose inflammation; Insulin resistance