Adverse effects of fructose in perfused livers of diabetic rats.

Livers isolated from both fed normal and alloxan diabetic rats were perfused for 30 min using Krebs-Henseleit bicarbonate blood buffer medium followed by 10 min flow-through infusions with either 5 mM or 28 mM fructose concentrations. In livers of normal and diabetic rats, both 5 mM and 28 mM fructose concentrations produced an elevation in tissue cyclic AMP levels, activation of glycogen phosphorylase, increased protein kinase activity, decreased tissue ATP levels, large increases in tissue fructose-1-phosphate, and variable effects upon glycogen synthase. These results are consistent with previously reported cyclic AMP mediated activation of glycogen phosphorylase by fructose via protein kinase in normal rat liver. In addition, both 5 mM and 28 mM fructose infusion resulted in large decreases in normal and diabetic synthase phosphatase activity. Therefore, these results in both normal and diabetic livers are inconsistent with a direct beneficial effect of fructose in the isolated perfused rat liver.