Figure 5. Working model depicting the underlying mechanism of 11β-HSD1- mediated insulin resistance.

Glucocorticoids (inactive) cause activation of 11β-HSD1 in adipocytes producing active glucocorticoids. Active glucocorticoid-GR signaling complex activates the JNK pathway. JNK then inhibits insulin-induced Akt phosphorylation leading to insulin resistance. JNK may also be activated by inflammatory cytokines such as Tumor necrosis factor-α. [GCs = glucocorticoids, GR = glucocorticoid receptor, IR = insulin receptor, JNK = c-Jun N-terminal kinase; site of action of various inhibitors is also shown (green text)].