Interestingly, although serine phosphorylation of IRS1 is usually regarded as being negatively regulatory for insulin signaling (36), multiple sites of serine phosphorylation of IRS1 were reduced in T2D iHeps compared with controls, suggesting that these are part of a normal feedback mechanism and that this mechanism may be lost in T2D. The gene discussed is INS; the disease is type 2 diabetes mellitus.