Decreased levels of total IRS1 in adipocytes has previously been reported in insulin-resistant subjects27 and led to impaired glucose uptake in a type 2 diabetes animal model.28 Collectively, these results suggest that an enhanced insulin signaling in the fat depots of Rptorob−/− mice may account for the higher peripheral sensitivity to insulin (Fig. 4g). This evidence concerns the gene IRS1 and type 2 diabetes mellitus.