INS and obesity due to melanocortin 4 receptor deficiency: In contrast, in obesity-associated T2DM, cortisol regeneration by 11βHSD1 in the whole body is increased while hepatic 11βHSD1 activity is unchanged compared with lean nondiabetic individuals (6, 12); because insulin suppresses hepatic 11β-HSD1 activity (13), the impaired insulin signaling associated with T2DM may drive the lack of suppression of hepatic 11βHSD1 in this group.