COMT and Insulin resistance: Indeed after a 2-week experimental period, metformin treatment did not inhibit insulin resistance (Fig. 4k), and neither the COMT inhibitor nor 2-ME treatment altered insulin resistance compared with metformin alone (Fig. 4k), suggesting that in this 2-week period the glucose-lowering effects of these compounds was mediated by altering insulin secretion but not by modifying the insulin resistance.