Response of hepatic fructokinase to long-term sucrose diets and diabetes in spiny mice, albino mice and rats

1. 1. The activity of hepatic fructokinase increased about 2-fold in desert-derived spiny mice (Acomys cahirinus) and laboratory bred albino mice and rats, maintained on a 50% sucrose diet for 3 months. 2. 2. The role of fructose as the specific inducer was apparent, as 25% fructose diet produced activity increases similar to those of sucrose in contrast to 25% glucose diet. 3. 3. The activity of hexokinase was not affected by the sucrose diet, that of glucokinase rose marginally but those of pyruvate kinase and NADP-malate dehydrogenase rose pronouncedly, especially in the spiny mice. 4. 4. Fructokinase activity increased significantly only after 2 weeks on the diet and continued to rise gradually. The activities of other glycolytic enzymes rose markedly already after 3 days and peaked at about 14 days. 5. 5. Fasting for 48 hr did not influence fructokinase activity while markedly reducing that of glucokinase, pyruvate kinase and NADP-malate dehydrogenase. 6. 6. Streptozotocin diabetes in rats resulted in a 40% reduction in fructokinase activity after 14 days which was restored after 6 days of insulin treatment. The activity increases of other glycolytic enzymes were more marked. However, the fructokinase induction on the sucrose diet was evident also in diabetic rats, suggesting that the insulin and substrate effects are independent. The preference of fructose over glucose phosphorylation capacity was clearly demonstrable in the non-diabetic and diabetic rats and became enhanced on sucrose feeding. 7. 7. The activity of triokinase also increased on the sucrose diet in the 3 rodent species, suggesting a coordinative substrate effect on the induction of these two rate-limiting fructolysis enzymes. 8. 8. It is concluded that the hepatic fructokinase, similarly to the intestinal fructokinase, should be regarded as an adaptive enzyme, responding to substrate availability and to endocrine changes.