AKR1B1 and Hyperglycemia: As has been observed in hyperglycaemia, increased glycolytic flux leads to a saturation of hexokinase, followed by shunting of as much as one-third of glucose through aldose reductase in the polyol pathway, which uses one mole of NADPH per mole glucose metabolized and generates one mole of NADH per mole of fructose produced from the intermediate sorbitol (Yabe-Nishimura, 1998).