MiR17 improves insulin sensitivity through inhibiting expression of ASK1 and anti-inflammation of macrophages.

OBJECTIVES: MicroRNAs (miRNAs) are involved in the pathological progression of various disease including type 2 diabetes (T2D). Chronic inflammation in adipose tissue is a cause of insulin resistance and T2D. MiR-17 palys an anti-inflammatory role in many biological processes. We hypothesized that miR-17 suppressed inflammatory macrophage that is related to insulin resistance in patients with T2D.

METHODS: Macrophage migration and secretion of inflammatory cytokines including TNF-α, IL-6 and IL-1β were detected through transwell migration assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was tested by the radioactivity of tritium-labeled glucose in 3T3-L1 adipocytes. Dual luciferase reporter gene assay was employed to evaluate the interaction between miR-17 and 3'UTR of ASK1.

RESULTS: Our results showed that miR-17 inhibited macrophage infiltration and secretion of TNF-α, IL-6 and IL-1β. Moreover, insulin-stimulated glucose uptake of 3T3-L1 was suppressed by treatment with LPS-induced macrophage conditioned media (CM), whereas the opposite effect was showed after treatment with the CM of macrophages transfected with miR-17. Furthermore, we found that miR-17 directly prevented expression of ASK1 by binding to its 3'UTR.

CONCLUSION: miR-17 improved inflammation-induced insulin resistance by suppressing ASK1 expression in macrophages. These results indicated that miR-17 had an anti-diabetic acitivity by its anti-inflammation effect on macrophage.