Effects of galactose on direct and indirect pathway estimates of hepatic glycogen synthesis

Hepatic glycogen is formed by direct and indirect pathways whose activities reflect altered nutrition or disease. Direct/indirect pathway measurements often involve test meals where ∼10% of carbohydrate is galactose, but its effects on direct/indirect pathway estimates are unknown. Therefore, direct/indirect pathway contributions in 24-h fasted rats given 2 g/kg 100% glucose (GLU, n=6) or 90% glucose–10% galactose (GLU+GAL, n=6) were measured by [U-13C]glucose dilution and by position-5/position-2 glycogen enrichment (H5/H2) from 2H2O. For GLU+GAL, galactose glycogenesis was independently measured with [1-13C]galactose. Glycogenesis was equivalent in both groups but for GLU+GAL, 23±4% of glycogen was derived from galactose. [U-13C]glucose reported a 30±3% direct pathway contribution to glycogenesis for GLU but only 20±3% for GLU+GAL (p=0.012 vs. GLU). H5/H2 yielded identical direct pathway estimates (32±3% GLU, 29±6% GLU+GAL). Thus, galactose glycogenesis was undetected by H5/H2 while [U-13C]glucose reported a reduced direct/indirect pathway ratio. With [1-13C]galactose also present, correct glycogenic source contributions were obtained.