Decreases in hepatic fructose-2,6-bisphosphate level and fructose-6-phosphate,2-kinase activity in diabetic mice: a close relationship to the development of ketosis.

Hyperglycemic mice with streptozotocin diabetes were divided into two groups according to the presence or absence of ketosis. No difference in blood glucose level between two groups was observed in this experiment. However, hepatic fructose-2,6-P2 level and fructose-6-P,2-kinase activity were decreased only in ketotic diabetic mice. Similar decreases in those indices were observed in 48-h starved normal mice. In ketotic diabetes, insulinization for 24 h was required to normalize fructose-2,6-P2 level and fructose-6-P,2-kinase activity, while glucose administration normalized altered fructose-2,6-P2 metabolism in starvation only in 30 min. Hepatic cyclic AMP was increased neither in ketotic nor in non-ketotic diabetic mice. These results indicate that the decrease in hepatic fructose-2,6-P2 level in diabetes is apparently related to the occurrence of ketosis, but not to hyperglycemia. The mechanisms of the decrease in fructose-6-P,2-kinase activity in ketotic diabetes and starvation are discussed.