Acetaminophen glucuronidation accurately reflects gluconeogenesis in fasted dogs

Area of Science:

• Metabolic research
• Animal physiology
• Biochemistry

Background:

• Gluconeogenesis is vital for maintaining blood glucose homeostasis during fasting.
• Uridyl diphosphate-glucose (UDP-glucose) is a key intermediate in glucose metabolism.
• Acetaminophen glucuronide is a potential biomarker for assessing glucose metabolism.

Purpose of the Study:

• To determine if acetaminophen glucuronide reflects uridyl diphosphate-glucose (UDP-glucose) derived from gluconeogenesis in fasted dogs.
• To investigate the impact of fasting duration on glucose flux and UDP-glucose metabolism.

Main Methods:

• Three mongrel dogs were infused with isotopes ([U-14C]lactate, [1-13C]galactose, [6-3H]glucose) after overnight or 2.5-day fasts.
• Acetaminophen was administered, and urinary acetaminophen glucuronide was isolated and analyzed.
• Plasma glucose flux and intrahepatic UDP-glucose flux were measured using isotopic tracers.

Main Results:

• Plasma [14C]glucose specific activity closely matched urinary acetaminophen glucuronide specific activity in both fasting states.
• Plasma glucose flux and intrahepatic UDP-glucose flux significantly decreased with prolonged fasting.
• Glucose cycling through UDP-glucose and glycogen diminished with extended fasting periods.

Conclusions:

• Acetaminophen glucuronide serves as an accurate indicator of gluconeogenesis and reflects UDP-glucose derived from the same glucose 6-phosphate pool in fasted dogs.
• Fasting duration significantly impacts glucose production and utilization pathways, with reduced flux observed during prolonged fasting.