title: 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 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.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: C
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: T
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: F
authors.initials: F
authors.lastname: Shen
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: X
authors.initials: X
authors.lastname: Gu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D054443:Cell Migration Assays; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology*; D007333:Insulin Resistance; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D018836:Inflammation Mediators; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide