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

Menthol glucuronlide was isolated from the urine of a healthy-70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-C-13]glucose. Glucuronide C-13-excess enrichment levels were 4-6% and thus provided high signa to-noise ratios (SNRs) for confident assignment of C-13-C-13 Spin-coupled multiplet components within each C-13 resonance by C-13 NMR. The [U-C-13]glucuronide isotopomer derived via dire pathway conversion of [U-C-13]glucose to [U-C-13] UDP-glucose was resolved from [1,2,3-C-13(3)]- and [1,2-C-13(2)]glucuronide is topomers derived via Cori cycle or indirect pathway metabolism of [U-C-13]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were give peppermint oil and infused with [U-C-13]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-C-13]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide C-13-isotopomers were analyzed by C-13 NMR. [U-C-13]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-C-13(3)] an [1,2-C-13(2)]glucuronide enrichments was 0.9% +/- 0.2%. Fro these data, flux of plasma glucose to hepatic UDPG was est mated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.