We have previously shown that the administration of a 10% w/v fructose solution to female rats caused hyperinsulinaemia, glucose intolerance, reduced insulin receptor substrate-2 (IRS-2) hepatic expression, and hepatic steatosis, which we attributed to the induction of carbohydrate response element binding protein (ChREBP)10, 11. Here, IRS2 is linked to fatty liver disease.