Testing of the assumptions made in estimating the extent of futile cycling

Am J Physiol. 1989 May;256(5 Pt 1):E668-75. doi: 10.1152/ajpendo.1989.256.5.E668.


In estimating glucose and fructose 6-phosphate futile cycling in vivo, complete detritiation of [2-3H]glucose is assumed at the glucose 6-phosphate level, [3-3H]glucose at triose phosphate formation, and [6-3H]glucose in its conversion to glucose via pyruvate. [3-3H]glucose detritiation via the pentose cycle is assumed to be negligible. Normal and non-insulin-dependent diabetic subjects, in the basal state and infused with glucose, were given [2-3H,2-14C]galactose, and 3H-to-14C ratios in blood glucose were determined. [2-3H,2-14C]glucose was given with acetaminophen, and 3H/14C in urinary glucuronide was determined. Detritiation at glucose 6-phosphate was approximately 80%. [3-3H,1-14C]fructose was infused, and 3H/14C was determined in blood glucose and urinary glucuronide. At triose phosphate, 75-90% of the 3H was removed. The pentose cycle contribution was only a few percent. [6-3H,6-14C]glucose was infused, and 3H/14C in blood lactate was determined. [3-3H,3-14C]lactate was infused, and ratios in blood glucose were determined. Maximally, 10% of 3H from [6-3H]glucose was retained. If glucose and galactose are metabolized in the same hepatic site(s), glucose conversion to three-carbon intermediates in the indirect pathway of glycogen formation occurs in extrahepatic tissue(s). Reported estimates of futile cycling, although qualitatively correct, quantitatively require correction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Carbon Radioisotopes
  • Diabetes Mellitus / metabolism
  • Fructosephosphates / metabolism
  • Galactose / metabolism
  • Glucose / metabolism*
  • Glucose-6-Phosphate
  • Glucosephosphates / metabolism
  • Glycogen / biosynthesis
  • Humans
  • Liver / metabolism
  • Male
  • Middle Aged
  • Pentose Phosphate Pathway
  • Tritium


  • Blood Glucose
  • Carbon Radioisotopes
  • Fructosephosphates
  • Glucosephosphates
  • Tritium
  • Glucose-6-Phosphate
  • fructose-6-phosphate
  • Glycogen
  • Glucose
  • Galactose