Uniquely, in the present study, we have demonstrated that pharmacologic activation of Nrf2 can reverse type 2 diabetes by performing metabolic analyses before and after 4−5 weeks therapeutic intervention with TBE-31 in adult Nrf2+/+ mice fed a HFFr diet, thereby providing clear evidence that the acetylenic tricyclic bis(cyano enone) can improve glucose disposal and insulin sensitivity. The gene discussed is INS; the disease is type 2 diabetes mellitus.