Acetaminophen glucuronidation accurately reflects gluconeogenesis in fasted dogs.
To assess whether acetaminophen glucuronide accurately reflects uridyl diphosphate-glucose (UDP-glucose) derived from gluconeogenesis during fasting, three mongrel dogs received infusions of [U-14C]lactate, [1-13C]galactose, and [6-3H]glucose (after fasting overnight or for 2.5 days). After initiation of the isotopes (3 h), acetaminophen was given, and the urinary acetaminophen glucuronide was isolated. The mean plasma [14C]glucose specific activity (SA) was similar to the mean urinary acetaminophen glucuronide SA both after fasting overnight [299 +/- 19 vs. 296 +/- 14 disintegrations.min-1 (dpm).mumol-1, respectively] and after 2.5 days of fasting (511 +/- 8 vs. 562 +/- 32 dpm/mumol, respectively). Mean plasma glucose flux calculated using [6-3H]glucose decreased (P < 0.05) with two additional days of fasting (18.7 +/- 1.2 vs. 13.6 +/- 0.6 mumol.kg-1.min-1), as did intrahepatic (P < 0.05) UDP-glucose flux measured using [1-13C]galactose (8.6 +/- 0.7 vs. 5.5 +/- 0.3 mumol.kg-1.min-1). We conclude that, in fasted dogs, plasma glucose and UDP-glucose, as sampled by acetaminophen, equally reflect gluconeogenesis and appear to come from the same pool of glucose 6-phosphate. In addition, cycling of glucose moieties through UDP-glucose and glycogen decreases with an increased period of fasting.
Schwenk
W F
WF
Department of Pediatrics, Mayo Clinic, Rochester, Minnesota 55905, USA.
Kahl
J C
JC
D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D015415:Biomarkers; D004285:Dogs; D005215:Fasting; D005260:Female; D005947:Glucose / Q000378:metabolism*; D014532:Uridine Diphosphate Glucose / Q000032:analysis*
D015415:Biomarkers; D000082:Acetaminophen; C037386:acetaminophen glucuronide; D005947:Glucose; D014532:Uridine Diphosphate Glucose