INS and obesity due to melanocortin 4 receptor deficiency: Most interestingly, despite increased hepatic Akt activity in these obesity models, the effect of Akt on FoxO1 phosphorylation and therefore gluconeogenic enzyme expression is compromised, and this leads to increases in hepatic glucose production, secondary increases in pancreatic insulin secretion, further increases in hepatic aPKC activity, and activation of aPKC-dependent lipogenic and proinflammatory factors.