title: Inflamed macrophage microvesicles induce insulin resistance in human adipocytes.
abstract: BACKGROUND
  Cytokines secreted by adipose tissue macrophages (ATMs) significantly alter adipocyte function, inducing inflammatory responses and decreasing insulin sensitivity. However, little relevant information is available regarding the role of microvesicles (MVs) derived from ATMs in macrophage-adipocyte crosstalk.
  
  
  METHODS
  MVs were generated by stimulation of M1 or M2 phenotype THP-1 macrophages and incubated with human primary mature adipocytes and differentiated adipocytes. Subsequently, insulin-stimulated phosphorylation of Akt (pAkt) and glucose uptake were determined. Glucose transporter 4 (GLUT4) translocation and nuclear translocation of nuclear factor (NF)-kappa B were also analyzed in treated adipocytes.
  
  
  RESULTS
  M1 macrophage-derived MVs (M1 MVs) significantly reduced protein abundance of insulin-induced Akt phosphorylation in human primary mature adipocytes and differentiated adipocytes, when compared with the same concentration of M2 macrophage-derived MVs (M2 MVs). In contrast to M2 MVs, which enhanced the insulin-induced glucose uptake measured by 2-NBDG, M1 MVs decreased this effect in treated adipocytes. M1 MVs treatment also brought about a significant increase in the nuclear translocation of nuclear factor (NF)-kappa B, coupled with a decrease in pAkt level and GLUT4 translocation compared with M2 MVs-treated adipocytes. These effects were reversed by BAY 11-7085, a NF- kappa B specific inhibitor.
  
  
  CONCLUSIONS
  MVs derived from proinflammatory (M1) macrophages may, at least in part, contribute to the pathogenesis of obesity-induced insulin resistance, reducing insulin signal transduction and decreasing glucose uptake in human adipocytes, through NF-kappa B activation. Therefore, these MVs may be potential therapy candidates for the management of type 2 diabetes mellitus.
authors.affiliation: The Affiliated Drum Tower Hospital of Nanjing Medical University, Nanjing, Jiangsu 21008 China.|Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Affiliated Drum Tower Hospital of Nanjing Medical University, Nanjing, Jiangsu 21008 China.|Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors.forename: Jiexin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: The Affiliated Drum Tower Hospital of Nanjing Medical University, Nanjing, Jiangsu 21008 China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Zhu
keywords: Human adipocyte; Insulin resistance; Macrophage; Microvesicle