title: Cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver.
abstract: When dietary carbohydrate is unavailable, glucose required to support metabolism in vital tissues is generated via gluconeogenesis in the liver. Expression of phosphoenolpyruvate carboxykinase (PEPCK), commonly considered the control point for liver gluconeogenesis, is normally regulated by circulating hormones to match systemic glucose demand. However, this regulation fails in diabetes. Because other molecular and metabolic factors can also influence gluconeogenesis, the explicit role of PEPCK protein content in the control of gluconeogenesis was unclear. In this study, metabolic control of liver gluconeogenesis was quantified in groups of mice with varying PEPCK protein content. Surprisingly, livers with a 90% reduction in PEPCK content showed only a approximately 40% reduction in gluconeogenic flux, indicating a lower than expected capacity for PEPCK protein content to control gluconeogenesis. However, PEPCK flux correlated tightly with TCA cycle activity, suggesting that under some conditions in mice, PEPCK expression must coordinate with hepatic energy metabolism to control gluconeogenesis.
authors.affiliation: The Advanced Imaging Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235-9085, USA. shawn.burgess@utsouthwestern.edu
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Burgess
authors.forename: TianTeng
authors.initials: T
authors.lastname: He
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Jill
authors.initials: J
authors.lastname: Lindner
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Browning
authors.forename: Mark A
authors.initials: MA
authors.lastname: Magnuson
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003600:Cytosol / Q000201:enzymology; D003903:Deuterium / Q000493:pharmacokinetics; D004734:Energy Metabolism / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D005943:Gluconeogenesis / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010730:Phosphoenolpyruvate Carboxylase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011849:Radioactive Tracers
chemical_list: D002250:Carbon Radioisotopes; D011849:Radioactive Tracers; D003903:Deuterium; D010730:Phosphoenolpyruvate Carboxylase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose