NOS3 and hyperuricemia: Possible mechanisms by which hyperuricaemia may cause or aggravate IR are as follows: (i) high UA levels reduce tissue phosphorylated protein kinase B (pAkt) levels, causing impairment of the protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) signalling pathway and resulting in decreased nitric oxide (NO) production, which decreases blood flow to skeletal muscle and reduces its uptake of glucose [54].