title: Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo.
abstract: The purpose of this study was to compare the assessment of gluconeogenesis (GNG) in the overnight- and prolonged-fasted states and during chronic hypercortisolemia using the arteriovenous difference and [14C]phosphoenolpyruvate-liver biopsy techniques as well as a combination of the two. Two weeks before a study, catheters and flow probes were implanted in the hepatic and portal veins and femoral artery of dogs. Animals were studied after an 18-h fast (n = 8), a 42- or 66-h fast (n = 7), and an 18-h fast plus a continuous infusion of cortisol (3.0 microg. kg(-1). min(-1)) for 72 h (n = 7). Each experiment consisted of an 80-min tracer ([3-(3)H]glucose and [U-(14)C]alanine) and dye equilibration period (-80 to 0 min) and a 45-min sampling period. In the cortisol-treated group, plasma cortisol increased fivefold. In the overnight-fasted group, total GNG flux rate (GNG(flux)), conversion of glucose 6-phosphate to glucose (GNG(G-6-P-->Glc)), glucose cycling, and maximal GNG flux rate (GNG(max)) were 0.95 +/- 0.14, 0.65 +/- 0.06, 0.62 +/- 0.06, and 0.70 +/- 0.09 mg. kg(-1). min(-1), respectively. In the prolonged-fasted group, they were 1.50 +/- 0.18, 1.18 +/- 0.13, 0.40 +/- 0.07, and 1.28 +/- 0.10 mg. kg(-1). min(-1), whereas in the cortisol-treated group they were 1.64 +/- 0.33, 0.99 +/- 0.29, 1.32 +/- 0.24, and 0.91 +/- 0.13 mg. kg(-1). min(-1). These results demonstrate that GNG(G-6-P-->Glc) and GNG(max) were almost identical. However, these rates were 15-38% lower than GNG(flux) generated by a combination of the two methods. This difference was most apparent in the steroid-treated group, where the combination of the two methods (GNG(flux)) detected a significant increase in gluconeogenic flux.
authors.affiliation: Department of Surgery, Vanderbilt University, and the Nashville VA Medical Center, Nashville, TN, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Goldstein
authors.forename: Luciano
authors.initials: L
authors.lastname: Rossetti
authors.forename: Brett A J
authors.initials: BA
authors.lastname: Palmer
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Duna
authors.initials: D
authors.lastname: Massillon
authors.forename: Melanie
authors.initials: M
authors.lastname: Scott
authors.forename: Doss
authors.initials: D
authors.lastname: Neal
authors.forename: Phillip
authors.initials: P
authors.lastname: Williams
authors.forename: Benjamin
authors.initials: B
authors.lastname: Peeler
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D002250:Carbon Radioisotopes; D004285:Dogs; D005215:Fasting / Q000502:physiology*; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D005990:Glycerol / Q000097:blood; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010728:Phosphoenolpyruvate / Q000493:pharmacokinetics; D010827:Physiology / Q000379:methods*
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D002250:Carbon Radioisotopes; D019344:Lactic Acid; D019298:Glucose-6-Phosphate; D010728:Phosphoenolpyruvate; D005990:Glycerol; D006854:Hydrocortisone