Autoregulation of glucose production in men with a glycerol load during rest and exercise

Abstract

Related to hepatic autoregulation we evaluated hypotheses that 1) glucose production would be altered as a result of a glycerol load, 2) decreased glucose recycling rate (Rr) would result from increased glycerol uptake, and 3) the absolute rate of gluconeogenesis (GNG) from glycerol would be positively correlated to glycerol rate of disappearance (Rd) during a glycerol load. For these purposes, glucose and glycerol kinetics were determined in eight men during rest and during 90 min of leg cycle ergometry at 45 and 65% of peak O2 consumption (V˙o 2 peak). Trials were conducted after an overnight fast, with exercise commencing 12 h after the last meal. Subjects received a continuous infusion of [6,6-2H2]glucose, [1-13C]glucose, and [1,1,2,3,3-2H5]glycerol without (CON) or with an additional 1,000 mg (rest: 20 mg/min; exercise: 40 mg/min) of [2-13C]- or unlabeled glycerol added to the infusate (GLY). Infusion of glycerol dampened glucose Rr, calculated as the difference between [6,6-2H2]- and [1-13C]glucose rates of appearance (Ra), at rest [0.35 ± 0.12 (CON) vs. 0.12 ± 0.10 mg · kg−1 · min−1 (GLY), P < 0.05] and during exercise at both intensities [45%: 0.63 ± 0.14 (CON) vs. 0.04 ± 0.12 (GLY); 65%: 0.73 ± 0.14 (CON) vs. 0.04 ± 0.17 mg · kg−1 · min−1 (GLY), P < 0.05]. Glucose Ra and oxidation were not affected by glycerol infusion at rest or during exercise. Throughout rest and both exercise intensities, glycerol Rdwas greater in GLY vs. CON conditions (rest: 0.30 ± 0.04 vs. 0.58 ± 0.04; 45%: 0.57 ± 0.07 vs. 1.19 ± 0.04; 65%: 0.73 ± 0.06 vs. 1.27 ± 0.05 mg · kg−1 · min−1, CON vs. GLY, respectively). Differences in glycerol Rd(ΔRd) between protocols equaled the unlabeled glycerol infusion rate and correlated with plasma glycerol concentration ( r = 0.97). We conclude that infusion of a glycerol load during rest and exercise at 45 and 65% ofV˙o 2 peak 1) does not affect glucose Ra or Rd, 2) blocks glucose Rr, 3) increases whole body glycerol Rd in a dose-dependent manner, and 4) results in gluconeogenic rates from glycerol equivalent to CON glucose recycling rates.