Acute depletion of hepatic PHD3 in mice has been shown to improve whole body insulin sensitivity and diabetes by stabilising HIF-2α, thereby enhancing Irs2 gene transcription and insulin-stimulated Akt activation and decreasing the expression of gluconeogenic genes such as G6pc, Pck1, and Ppargc1a in the liver31. This evidence concerns the gene IRS2 and diabetes mellitus.