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-C-14]lactate, [1 -C-13]galactose, and [6-H-3]glucose (after fasting overnight or for 2. 5 days). After initiation of the isotopes (3 h), acetaminophen was giv en, and the urinary acetaminophen glucuronide was isolated. The mean p lasma [C-14]glucose specific activity (SA) was similar to the mean uri nary acetaminophen glucuronide SA both after fasting overnight [299 +/ - 19 vs. 296 +/- 14 disintegrations . min(-1) (dpm).mu mol(-1), respec tively] and after 2.5 days of fasting (511 +/- 8 vs. 562 +/- 32 dpm/mu mol, respectively). Mean plasma glucose flux calculated using [6-H-3] glucose decreased (P < 0.05) with two additional days of fasting (18.7 +/- 1.2 vs. 13.6 +/- 0.6 mu mol . kg(-1). min(-1)), as did intrahepat ic (P < 0.05) UDP-glucose flux measured using [1-C-13]galactose (8.6 /- 0.7 vs. 5.5 +/- 0.3 mu mol . kg(-1). min(-1)). We conclude that, in fasted dogs, plasma glucose and UDP-glucose, as sampled by acetaminop hen, 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.