Type 2 diabetes as a redox disease

[...]metformin alone can attenuate much of the oxidative effect of exercise.7 The reason why exercise and metformin have opposing physiological consequences (oxidative vs reducing) has been shown by studies8 that suggest that giving mice metformin increases synthesis of the transcription factor Nrf2, which controls the downstream synthesis of RNA molecules coding for major cellular antioxidant enzymes. Compelling evidence that reductive redox potentials might be the molecular essence of type 2 diabetes first came to my attention in early 2013 when I learned from a 2009 German study that consumption of physiological amounts of the antioxidants vitamin C and vitamin E abrogated the capacity of physical exercise to make insulin more effective in lowering blood sugar concentrations.7,9 This finding is supported by similar studies of other antioxidants in man.10-12 Further suggestive evidence for the importance of an oxidative environment for promoting the action of insulin comes from patients with rare mutations impairing the production of antioxidant selenoproteins.