Sources of hepatic glycogen synthesis during an oral glucose tolerance test: Effect of transaldolase exchange on flux estimates

✍ Scribed by Teresa C. Delgado; Claúdia Silva; Isabel Fernandes; Madalena Caldeira; Margarida Bastos; Carla Baptista; Manuela Carvalheiro; Carlos F. G. C. Geraldes; John G. Jones

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 469 KB
• Volume: 62
• Category: Article
• ISSN: 0740-3194
• DOI: 10.1002/mrm.22107

✦ Synopsis

Abstract

Sources of hepatic glycogen synthesis during an oral glucose tolerance test were evaluated in six healthy subjects by enrichment of a 75‐g glucose load with 6.67% [U‐^13^C]glucose and 3.33% [U‐^2^H~7~]glucose and analysis of plasma glucose and hepatic uridine diphosphate–glucose enrichments (sampled as urinary menthol glucuronide) by ^2^H and ^13^C nuclear magnetic resonance. The direct pathway contribution, as estimated from the dilution of [U‐^13^C]glucose between plasma glucose and glucuronide, was unexpectedly low (36 ± 5%). With [U‐^2^H~7~]glucose, direct pathway estimates based on the dilution of position 3 ^2^H‐enrichment between plasma glucose and glucuronide were significantly higher (51 ± 6%, P = 0.05). These differences reflect the exchange of the carbon 4, 5, and 6 moiety of fructose‐6‐phosphate and glyceraldehyde‐3‐phosphate catalyzed by transaldolase. As further evidence of this exchange, ^2^H‐enrichments in glucuronide positions 4 and 5 were inferior to those of position 3. From the difference in glucuronide positions 5 and 3 enrichments, the fraction of direct pathway carbons that experienced transaldolase exchange was estimated at 21 ± 4%. In conclusion, the direct pathway contributes only half of hepatic glycogen synthesis during an oral glucose tolerance test. Glucose tracers labeled in positions 4, 5, or 6 will give significant underestimates of direct pathway activity because of transaldolase exchange. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.