The following are the supplementary data related to this

The following are the supplementary data related to this article.
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Acknowledgements The authors thank Dr. D. R. Kaplan for kind advice and materials derived from NB primary cell lines, Dr. F. D. Miller for PNC protein, Dr. H. Ichijo for ASK1 plasmids, and the Proteomics Core Facility at Sahlgrenska Academy for technical assistance. We also thank the Flow Cytometry Core Facility at the Clinical Chemistry Department, Sahlgrenska University Hospital. This work was supported by grants from the Swedish Childhood Cancer Foundation (IM2013-0007), the BioCARE (a National Strategic Research Program at the University of Gothenburg) (2010-1974-77049-33), the Västra Götaland Region County Council (ALF) (ALFGBG-211131), the Swedish Brain Foundation (FO2014-0049), the Åhlén Foundation (mB9/h12), and the Adlerbertska Foundation (E2012/36).
Introduction Type 2 diabetes (T2D) is characterized by chronic corticotropin releasing factor [1]. Adipose tissue macrophages (ATMs) promote chronic inflammatory responses by the release of inflammatory cytokines [2,3], which plays an important role in development of T2D. Macrophages are commonly polarized, which include M1 and M2 phenotypes [4]. Usually, local microenvironments are key regulators of transition between M1 and M2 phenotypes [5,6]. Activation of M1 macrophages secretes inflammatory cytokines and promotes pro-inflammatory responses. Alternatively, activation of M2 macrophages plays an anti-inflammatory role. The transition of macrophage polarization regulates the development of T2D. It has been reported that chronic inflammation was caused by an imbalanced M1/M2 ratio in adipose tissue of T2D patients [1]. Obesity-related insulin resistance causes and promotes diabetic pathophysiology [7]. Activation of M1 macrophages is associated with insulin resistance in obesity individuals [1,8,9]. At the beginning of T2D, macrophages infiltrated into adipose tissue and induced inflammatory response [10]. M1 macrophages secrete inflammatory cytokines including Interleukin-6 (IL-6), IL-1β and tumor necrosis factor (TNF)-α disturb insulin signaling, which then lead to insulin resistance [4,10]. Conversely, M2 macrophages promote insulin-dependent glucose uptake by producing anti-inflammatory cytokines [11]. MicroRNAs (miRNAs) are small noncoding RNAs (∼19–25 nucleotides) that completely or partially paired with 3′untranslated region (3′UTR) of their targeting mRNA, and then lead to post-transcriptional gene repression by promoting mRNA degradation and/or inhibiting translation [12]. miRNAs were involved in various physiological and pathological process including obesity, insulin resistance, inflammation, diabetes and metabolic syndrome [[13], [14], [15]]. It has been reported that dysregulation of miRNAs in peripheral blood mononuclear cells (PBMC) regulates the development of diabetes [16,17]. MiR-17–92 is located in the C13orf25 (chromosome 13 open reading frame 25) that also was named locus of MIR17HG (miR-17–92 cluster host gene). The miR-17–92 cluster is transcribed from the same promoter. As a polycistronic primary transcript, it encodes six miRNAs including miR-17, miR-18a, miR-19a, miR-20a, miR-19b, and miR-92 [18]. MiR-17–92 was found to be implicated in inflammatory response [18,19]. It has been reported that Inhibition of miR-17-5p inhibits the activation of macrophage in type 2 diabetes mellitus patients [20]. Moreover, miR-17-5p alleviates the suppressive function of myeloid-derived suppressor cells by directly blocking expression of STAT3 [21] that is a majior regulatory pathway of macrophage activation. ASK1 also regulates activation of macrophage [22]. Although miR-17 downregulation activated ASK1 pathway and led to neural stem cell apoptosis [23], the connection between miR-17 and ASK1 in diabetic inflammation and macropahge activation is still unknown. In the current study, we discuss the possible effects of miR-17 in macrophages-associated inflammation that might lead to insulin resistance and T2D. Our data suggested that miR-17 might be a key linker between obesity-associated inflammation and insulin resistance, which provide new the biological mechanism of inflammation mediated T2D.