INS and Hyperinsulinemia: At the same time, the impaired signaling, e.g., decreased AKT activity, may be more closely linked to the loss of regulation of gluconeogenesis, creating a pattern of “selective insulin resistance.” In vivo, chronic hyperinsulinemia and altered substrate supply from overnutrition may also play significant roles in these divergent responses (82), but the differential response of iHeps from T2D patients to insulin action on PCK1 and FASN expression indicates that at least part of this difference in response is cell intrinsic.