The cerebrospinal fluid (CSF) concentration of fructose is elevated in diabetes. In the alloxan-diabetic animal this elevation has been attributed to increased fructose production by the brain. The present study seeks to determine if the increased fructose production is due to hyperglycemia or insulin deficiency. C-14-fructose was injected into the CSF in anesthetized dogs, and from its rate of removal the turnover of CSF fructose was calculated. Since plasma fructose does not pass readily into CSF, the fructose flux reflects fructose production by brain.
In dogs made diabetic with growth hormone, which results in hyperglycemia and hyperinsulinism, CSF fructose levels and turnover rate are significantly elevated. Restoration of normoglycemia by a thirty-six hour fast returns CSF fructose levels to normal. Glucose infusion to elevate plasma glucose for four hours in normal dogs raises plasma fructose but not CSF fructose levels. Similarly, eliminating hyperglycemia for three hours in alloxan-diabetic dogs by insulin infusion decreases plasma fructose, but CSF fructose levels remain elevated. Daily insulin injections do restore CSF fructose to normal.
It appears that increased fructose production by the brain in diabetes depends on hyperglycemia and the underlying metabolic processes for this require a number of hours to develop or be expressed.