Abstract
The incidence of obesity has increased rapidly, becoming a worldwide public health issue that involves insulin resistance. A growing number of recent studies have demonstrated that microRNAs play a significant role in controlling the insulin signaling network. For example, miR-506-3p expression has been demonstrated to correlate with insulin sensitivity; however, the underlying mechanism remains unknown. In this study, we found that miR-506-3p enhanced glucose uptake by 2-deoxy-D-glucose uptake assays and regulated the protein expression of key genes involved in the PI3K/AKT insulin signaling pathway including IRS1, PI3K, AKT, and GlUT4. We next predicted ribosomal protein S6 kinase B1 (S6K1) to be a candidate target of miR-506-3p by bioinformatics analysis and confirmed using dual-luciferase assays that miR-506-3p regulated S6K1 expression by binding to its 3′-UTR. Moreover, modulating S6K1 expression counteracted the effects of miR-506-3p on glucose uptake and PI3K/AKT pathway activation. In conclusion, miR-506-3p altered IR in adipocytes by regulating S6K1-mediated PI3K/AKT pathway activation. Taken together, these findings provide novel insights and potential targets for IR therapy.
Highlights
Highlights MicroRNAs is an important member of the regulatory network of insulin signaling pathway. Overexpression of miR-506-3p promotes glucose uptake in human adipocytes. MiR-506-3p could increase the sensitivity of adipocytes to insulin through S6 kinase B1 (S6K1) mediated insulin receptor substrate 1 (IRS1)/PI3K/AKT signaling pathway, which might afford novel insights and potential target for insulin resistance therapyThe rate of obesity has increased dramatically worldwide, recently becoming a dominant public health issue (Peters et al 2018; Reilly 2017)
type 2 diabetes mellitus (T2DM) has been investigated in many ways including proteomics, metabolomics, and metagenomics (Wang et al 2018), all of which have indicated that obesity-induced insulin resistance (IR) is the primary cause of T2DM (Marchesini et al 2008; Mozaffarian 2016)
We investigated the function of miR-506-3p in adipocytes and determined that the miR-506-3p/S6K1/ PI3K axis regulates glucose uptake in adipocytes
Summary
The rate of obesity has increased dramatically worldwide, recently becoming a dominant public health issue (Peters et al 2018; Reilly 2017). There is sufficient evidence to conclude that obesity is a risk factor for type 2 diabetes mellitus (T2DM) (Ghaben and Scherer 2019). T2DM is a common metabolic disease that can cause multiple complications in diverse organs (Wu et al 2018), these are divided into acute and chronic complications and both lead to poor quality of life and high mortality rates among diabetics. T2DM has been investigated in many ways including proteomics, metabolomics, and metagenomics (Wang et al 2018), all of which have indicated that obesity-induced insulin resistance (IR) is the primary cause of T2DM (Marchesini et al 2008; Mozaffarian 2016). IR is defined as decreased glucose availability due to the ineffectiveness of insulin, which leads to decompensation (Kabadi 2017; Petersen and Shulman 2018). As a critical characteristic of metabolic syndrome, impaired glucose uptake by adipocytes is closely related to
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