INS and Insulin resistance: Further suppression of COMT in HFD-fed and in pregnant mice was associated with glucose tolerance defects; however, in contrast to our hypothesis, 2-ME displayed distinct roles in the amelioration of glucose tolerance, which included (1) amelioration of insulin resistance (long-term HFD and COMT inhibitor-treated control-fed male mice or pregnant mice) and (2) induction of insulin secretion.