Noninvasive tracing of human liver metabolism: comparison of phenylacetate and apoB-100 to sample glutamine.
The labeling pattern of hepatic glutamine during infusion of [3-13C]lactate provides information on liver intermediary metabolism and allows us to correct apparent gluconeogenic rates for isotopic dilution in the oxaloacetate (OAA) pool. Liver glutamine can be sampled by its conjugation with phenylacetate to form phenylacetylglutamine (PAGN) but also by purifying the glutamine of the apolipoproteinB-100 of very low-density lipoprotein (apoB-100-VLDL). We compared these methods in normal and non-insulin dependent diabetes subjects. We tested also whether apoB-100-VLDL alanine enrichment could solve the problem of dilution of gluconeogenic precursor enrichments between peripheral blood and liver (prehepatic dilution). In both normal and diabetic subjects, the labeling patterns of glutamine obtained from PAGN or apoB-100-VLDL were comparable. Therefore, metabolic fluxes and correction factors for dilution in the OAA pool were also comparable. With both methods, gluconeogenic rates were not increased in diabetic patients. Use of the enrichment of apoB-100-VLDL alanine to correct for prehepatic dilution led to high estimates of gluconeogenesis; it remains uncertain whether this enrichment provides a correct estimate of liver pyruvate enrichment.
Diraison
F
F
Institut National de la Santé et de la Recherche Médicale U499, Faculté Laennec, 69008 Lyon, France.
Large
V
V
Maugeais
C
C
Krempf
M
M
Beylot
M
M
D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D005973:Glutamine / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010648:Phenylacetates / Q000378:metabolism*; D012016:Reference Values
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001786:Blood Glucose; D006728:Hormones; D010648:Phenylacetates; D005973:Glutamine; D019344:Lactic Acid; C025136:phenylacetic acid