Previous studies found a potent insulin-mediated and glucose-dependent upregulation of NPRC,14,15 and in the current study, we found the expression of PPAR-gamma, a key regulator of glucose and lipid metabolism, was substantially upregulated in the aortic tissue of NPRC−/−ApoE−/− mice (Fig. 6F–J), which suggested a close relation between NPRC and metabolic disease such as AS. Here, INS is linked to metabolic disease.