Class 1C phosphosites, i.e., those that were increased by insulin stimulation in T2D iHeps by greater than 1.5-fold and with a P value of less than 0.05 but with little or no change in control cells, were enriched for phosphosites on a third subset of proteins involved in Rho-GTPase signaling but different from those in classes 1B and 2B, which showed impaired or defective phosphorylation, as well as enrichment for proteins involved in vesicle-mediated transport, metabolism of RNA, mTOR signaling, and regulation of PTEN (Figure 4, C and E). This evidence concerns the gene INS and type 2 diabetes mellitus.