Measurement on gluconeogenesis during rest and exercise: A comparison of methods and carbon-13 recovery

Related to hepatic autoregulation and glucose production, including a methodological critique, we evaluated the hypotheses that: (1) a glycerol load would alter glucose production, (2) increased glycerol uptake would dampen glucose recycling, (3) increased gluconeogenesis (GNG) would maintain euglycemia during fasting rest, and (4) increased glycogenolysis and gluconeogenesis would augment hepatic glucose production (HGP) during exercise. For these purposes men were studied following an overnight fast during rest and 90 min of leg cycle ergometry at 45 and 65% V˙O2peak. Subjects received 1 of 6 isotope infusion protocols (Px) containing [6,6- 2H]glucose and either: (1) [1-13C]glucose, and [1,1,2,3,3-2H]glycerol without or (2) with an additional 1,000 mg of unlabeled glycerol added to the infusate, (3) [213 C]glycerol, (4) NaH13CO3, (5) [1- 13C]acetate, or (6) [2-13C] acetate.;Glucose rate of appearance (Ra) and disappearance (R d) increased during the transition from rest to exercise in an intensity dependent manner. Moreover, glucose Ra, and Rd were similar among the different infusion protocols during rest and exercise. Glucose recycling rate (Rr) was reduced during infusion P2 compared to P1 at rest and during both exercise intensities. Glycerol rate of disappearance (Rd) was greater in P2 compared to P1 conditions and was comparable to the unlabeled glycerol infusion rate (r = 0.97).;The relative gluconeogenic (f) rate increased over time at rest (P3). However, the time-dependent increase in f was not observed during exercise at 45 or 65% V˙O2peak. Moreover, at 65% V˙O2peak, f decreased compared to rest and 45 V˙O2peak, respectively. However, absolute gluconeogenesis (GNGab), increased during exercise compared to rest.;We conclude that: (1) hepatic glucose production scales to exercise intensity, (2) exogenous glycerol blocks glucose recycling, but does not affect glucose Ra or Rd; (3) increased gluconeogenesis maintains hepatic glucose production at rest, (4) f is reduced during light and moderate exercise, and (5) the effects of exercise on gluconeogenesis are time and intensity dependent.