On the other hand, it is also clear that a primary defect in insulin action specifically in muscle, as has been produced experimentally by muscle-specific knockout of either the insulin receptor [8] or PKC-λ [9] can cause systemic insulin resistance, hyperinsulinemia and secondary increases in hepatic aPKC activity, that in turn lead to increases in lipogenic and gluconeogenic enzymes, and, thus, initially, to development of metabolic syndrome features of abdominal obesity, hepatosteatosis and hyperlipidemia, and, later, to development of overt T2DM [10]. This evidence concerns the gene INS and hyperinsulinism.