LncRNA SOX2OT improves insulin resistance in type 2 diabetes with sleep disorders by activating IRS/PI3K/AKT and suppressing oxidative stress and inflammation through the miR-552-5p/SOX2 axis.

Abstract

Obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) frequently co-occur, with long noncoding RNAs (lncRNAs) implicated in their shared pathophysiology (T2DM-OSA). LncRNA sex determining region Y-box protein 2 (SOX2) overlapping transcript (SOX2OT) is downregulated in diabetic models. This study investigated SOX2OT's regulatory roles using in vivo and in vitro T2DM-OSA models. Intermittent hypoxia (IH) and high glucose (HG) significantly suppressed SOX2OT expression in murine systems and HepG2 hepatocytes. SOX2OT overexpression enhanced glucose consumption and uptake in HG/IH-treated cells by activating insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B (IRS/PI3K/AKT) signaling. Concurrently, SOX2OT attenuated oxidative stress (reactive oxygen species (ROS), malondialdehyde (MDA)) while elevating antioxidant activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), and suppressed inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)). Mechanistically, SOX2OT functioned as a competing endogenous RNA for microRNA-552-5p (miR-552-5p) to depress SOX2 expression. Crucially, SOX2 knockdown abolished SOX2OT-mediated cytoprotection. Thus, SOX2OT ameliorates insulin resistance in T2DM-OSA through IRS/PI3K/AKT activation and miR-552-5p/SOX2-mediated suppression of oxidative stress and inflammation.