Our findings demonstrated that altered glucose uptake and HBP shunt contributed to the increased O-linked N-Acetylglucosamine (O-GlcNAc) transferase expression and activity, which was associated with increased O-GlcNAc levels in pulmonary arterial smooth muscle cell and endothelial cells (PASMCs and PAECs, respectively), PASMC proliferation, and IPAH clinical worsening. The gene discussed is OGT; the disease is idiopathic pulmonary arterial hypertension.