Effects of fructose on hepatic glucose metabolism.
OBJECTIVE
The liver plays an important role in glucose tolerance. A number of studies have suggested fructose improves glucose tolerance especially in insulin resistant settings. This review summarizes the recent work suggesting that fructose enhances glucose tolerance by augmenting liver glucose uptake. This increase may be mediated by the translocation and activation of hepatic glucokinase.


RESULTS
Catalytic quantities of fructose (<10% of total carbohydrate flux) enhance liver glucose uptake in a dose dependent manner. The primary fate of the glucose is glycogen synthesis. The ability of fructose to augment liver glucose uptake is not impaired by the presence of marked insulin resistance such as in type 2 diabetes or infection. In addition, it is able to further enhance liver glucose uptake in the normal adapted setting of total parenteral nutrition and reverse the infected-induced decrease in liver glucose uptake. Studies also demonstrate that the beneficial effects of fructose on liver glucose uptake during chronic nutritional support do not persist.


CONCLUSIONS
Fructose is a potent acute regulator of liver glucose uptake and glycogen synthesis. Inclusion of catalytic quantities of fructose in a carbohydrate meal improves glucose tolerance. This improvement is primarily mediated by the activation of hepatic glucokinase and consequent facilitation of liver glucose uptake. The improvement in glucose tolerance is most evident in insulin resistant settings (e.g. Type 2 diabetes and infection). The beneficial effect of fructose on hepatic glucose disposal, however, does not persist if fructose is given continuously such as in total parenteral nutrition.
McGuinness
Owen P
OP
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-7236, USA. owen.mcguinness@vanderbilt.edu
Cherrington
Alan D
AD
D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000494:pharmacology*; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis; D010289:Parenteral Nutrition, Total
D008112:Liver Glycogen; D005632:Fructose; D005941:Glucokinase; D005947:Glucose