Limitations in the use of [2-14C]acetate for measuring gluconeogenesis in vivo.
This study was undertaken to test two assumptions critical for use of [2-14C]acetate to measure gluconeogenesis in vivo. For the assumption that incorporation into glucose of products of [14C]acetate metabolism does not affect the distribution of label within the glucose molecule, we infused [2-14C]acetate in 17 healthy subjects and [3-14C]lactate in 10 healthy subjects and compared the ratio of the resultant specific activities of plasma glucose carbons 1, 2, 5, 6, and 3, 4 obtained with each tracer. The ratio obtained with [2-14C]acetate (2.99 +/- 0.07) was significantly different from the ratio obtained with [3-14C]lactate, (3.82 +/- 0.2, P < 0.01). Because the model predicts that these ratios should be identical, these results indicate that either the model is incorrect or that metabolism of [14C]acetate to other compounds affects the distribution of the label within the glucose molecule. To test the assumption that plasma 3-OH-butyrate specific activity approximates the specific activity of hepatic intramitochondrial acetyl CoA, we compared the ratio of specific activities of plasma glucose and 3-OH-butyrate obtained in 7 healthy subjects infused with [2-14C]acetate and [2-14C]octanoate. The ratio obtained with [2-14C]acetate (0.18 +/- 0.03) was significantly different from that obtained with [2-14C]octanoate, (0.10 +/- 0.02), P < 0.001. These results suggest compartmentalization of acetyl CoA within liver mitochondria and indicate that plasma 3-OH-butyrate specific activity may not necessarily approximate intramitochondrial acetyl CoA specific activity during [2-14C]acetate infusion. We conclude that assumptions critical for use of [2-14C]acetate to measure gluconeogenesis in vivo are not valid.
Consoli
A
A
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7886.
Nurjhan
N
N
Capani
F
F
Pangburn
T
T
Lapenna
D
D
Gerich
J
J
D020155:3-Hydroxybutyric Acid; D000085:Acetates / Q000008:administration & dosage / Q000378:metabolism*; D019342:Acetic Acid; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002210:Caprylates / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D005943:Gluconeogenesis; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007262:Infusions, Intravenous; D007773:Lactates / Q000097:blood; D008297:Male; D011865:Radioisotope Dilution Technique; D012016:Reference Values
D000085:Acetates; D001786:Blood Glucose; D002210:Caprylates; D002250:Carbon Radioisotopes; D006885:Hydroxybutyrates; D007773:Lactates; C031492:octanoic acid; D019342:Acetic Acid; D020155:3-Hydroxybutyric Acid