Testing of the assumptions made in estimating the extent of futile cycling.
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.
Wajngot
A
A
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Chandramouli
V
V
Schumann
W C
WC
Kumaran
K
K
Efendić
S
S
Landau
B R
BR
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002250:Carbon Radioisotopes; D003920:Diabetes Mellitus / Q000378:metabolism; D005636:Fructosephosphates / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010427:Pentose Phosphate Pathway; D014316:Tritium
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D005636:Fructosephosphates; D005958:Glucosephosphates; D014316:Tritium; D019298:Glucose-6-Phosphate; C027618:fructose-6-phosphate; D006003:Glycogen; D005947:Glucose; D005690:Galactose