Acetaminophen glucuronidation accurately reflects gluconeogenesis in fasted dogs

Abstract

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.

Sources of hepatic glucose production by 2H2O ingestion and Bayesian analysis of 2H glucuronide enrichment

“…Hence, the ratios of 2 H enrichment in positions 5 and 2 (H5/H2) of G6P and plasma glucose reflect the fractional contribution of gluconeogenesis to fasting GP. The glucuronide moiety of acetaminophen is assumed to be derived from a hepatic uridine diphosphate (UDP)‐glucose pool that is in isotopic steady state with hepatic G6P as a result of rapid G6P‐G1P exchange (18). On this basis, glucuronide H5/H2 is identical to that of hepatic G6P, and the fractional contributions of glycogenolysis and gluconeogenesis to GP are given by the following equations: The H5/H2 parameter is thus obtained from the ratio of the glucuronide 2 H NMR signals for these positions.…”

Vom Heilfasten zur Detox-Kur: Entwicklung neuer Konzepte zur besseren «Entschlackung»

“…UDP-Glucose nimmt bei fastenden Ratten auf etwa 60% ab. Beim fastenden Hund erfolgt die Glucuronidierung von Paracetamol entsprechend der verfügbaren UDP-Glycose [8,9]. Eine Hypoxie scheint die Glucuronidierung stark zu hemmen, was die Bedeutung von Leberdurchblutung und systemischer Durchblutung und Atmung beim Fasten unterstreicht [10].…”

Hepatic UDP‐glucose 13C isotopomers from [U‐13C]glucose: A simple analysis by 13C NMR of urinary menthol glucuronide

“…The hepatic uridine diphosphate glucose (UDPG) pool is a strategic site for sampling tracers of human hepatic carbohydrate metabolism (1–4). During feeding, there is net hepatic glycogen synthesis from both glucose and gluconeogenic substrates.…”