title: Increased hepatic fructose 2,6-bisphosphate after an oral glucose load does not affect gluconeogenesis.
abstract: The generally accepted metabolic concept that fructose 2,6-bisphosphate (Fru-2,6-P2) inhibits gluconeogenesis by directly inhibiting fructose 1,6-bisphosphatase is based entirely on in vitro observations. To establish whether gluconeogenesis is indeed inhibited by Fru-2,6-P2 in intact animals, a novel NMR method was developed using [U-13C]glucose and 2H2O as tracers. The method was used to estimate the sources of plasma glucose from gastric absorption of oral [U-13C]glucose, from gluconeogenesis, and from glycogen in 24-h fasted rats. Liver Fru-2,6-P2 increased approximately 10-fold shortly after the glucose load, reached a maximum at 60 min, and then dropped to base-line levels by 150 min. The gastric contribution to plasma glucose reached approximately 50% at 30 min after the glucose load and gradually decreased thereafter. Although the contribution of glycogen to plasma glucose was small, glucose formed from gluconeogenesis was substantial throughout the study period even when liver Fru-2,6-P2 was high. Liver glycogen repletion was also brisk throughout the study period, reaching approximately 30 micromol/g at 3 h. These data demonstrate that Fru-2,6-P2 does not inhibit gluconeogenesis significantly in vivo.
authors.affiliation: The Mary Nell and Ralph B. Rogers Magnetic Resonance Center, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
authors.forename: Eunsook S
authors.initials: ES
authors.lastname: Jin
authors.forename: Kosaku
authors.initials: K
authors.lastname: Uyeda
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Burgess
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
mesh_terms: D000042:Absorption; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002247:Carbon Isotopes; D003903:Deuterium; D005635:Fructosediphosphates / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage*; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D002247:Carbon Isotopes; D005635:Fructosediphosphates; D014867:Water; C027652:fructose 2,6-diphosphate; D006003:Glycogen; D003903:Deuterium; D005947:Glucose