Figure 6. Proposed mechanism of lipid-induced hepatic insulin resistance.

In normal, insulin-sensitive liver (left), Thr¹¹⁶⁰ does not interfere with IRK activation, and downstream signaling proceeds normally upon insulin binding. In NAFLD (right), DAG accumulation promotes membrane translocation of PKCε, which in turn phosphorylates INSR Thr¹¹⁶⁰ to impair IRK activity and thereby induces hepatic insulin resistance. Y, tyrosine; P, phosphate.