Gestational diabetes mellitus (GDM) is the primary cause of maternal and fetal morbidity and mortality. Insulin resistance (IR) is pivotal to GDM pathogenesis, and mammalian target of rapamycin (mTOR) is a critical regulator of GDM. An increasing amount of evidence indicates that vitamin D deficiency is a risk factor for GDM. However, there are few reports on the effect of IR on GDM placentas. The present study aims to verify that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) can ameliorate trophoblast IR by suppressing mTOR signaling. An IR BeWo cell model was established in the presence of high insulin and glucose medium. The IR level and mTOR activation with or without 1,25(OH)2D3 treatment were evaluated. The IR cells exhibited excessive mTOR signaling activation, upregulated inflammatory factor levels, and extensive lipid infiltration. However, 1,25(OH)2D3 reversed mTOR activation and reduced the IR level and lipid infiltration. In addition, 1,25(OH)2D3 treatment in GDM placental explants blocked the aberrant, increased levels of leptin, TNF-α, and IL-6. Therefore, 1,25(OH)2D3 treatment protects trophoblasts against high IR mainly through suppressing mTOR signaling, and this mechanism may serve as a potential therapy for patients with GDM.
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