The Impact of Dibutyl Phthalate on Insulin Signaling in Human Skeletal Muscle Cells.

Abstract

Background: In China, the environmental concern of Dibutyl Phthalate (DBP) exposure significantly endangers human health by inducing insulin resistance (IR). Skeletal muscle tissue plays a critical role in this process. However, the precise molecular mechanisms through which DBP interferes with the insulin signaling pathway remain to be fully elucidated. This study aims to explore the molecular mechanisms by which DBP induces IR in skeletal muscle, focusing on the phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT)-glucose transporter 4 (GLUT4) signaling pathway.

Methods: To investigate the molecular mechanisms underlying DBP-induced IR, an experimental study was established on a human skeletal muscle cell line (HSkMC). Expression levels of mRNA and proteins associated with key signaling genes within the insulin receptor (INSR)-insulin receptor substrate (IRS)-PI3K-AKT-GLUT4 pathway were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot techniques. Additionally, this study explored the effects of DBP alone and in combination with a PI3K inhibitor (BKM120) or phosphatase and tensin homolog (PTEN) overexpression lentivirus on these signaling components.

Results: Results from this study demonstrated that DBP exposure significantly decreased mRNA levels of INSR, IRS1, PI3K, AKT2, and GLUT4 in HSkMC cells compared to untreated control cells. This reduction was exacerbated when DBP was combined with BKM120 or PTEN overexpression lentivirus, suggesting a synergistic effect. Furthermore, DBP treatment reduced the expression and phosphorylation of AKT2, indicating a disruption in the insulin signaling pathway.

Conclusions: This study elucidates a molecular mechanism by which DBP induces IR in skeletal muscle cells, primarily through the deregulation of the PI3K-dependent insulin signaling pathway. These insights enhance comprehension of the pathophysiological changes associated with IR caused by environmental pollutants like DBP, potentially guiding future strategies for prevention and intervention.