title: Influence of liver triglycerides on suppression of glucose production by insulin in men.
abstract: BACKGROUND
  The ability of insulin to suppress hepatic glucose production is impaired among subjects with increased intrahepatic triglycerides (IHTG). However, little is known about the roles of insulin on the supporting fluxes of glucose production among patients with fatty liver.
  
  
  OBJECTIVE
  To evaluate the effects of insulin on fluxes through the three potential sources of plasma glucose (glycerol, the citric acid cycle, and glycogen) among patients with fatty liver. Design, Settings, Participants, and Intervention: Nineteen men with a range of IHTG (∼0.5% to 23%) were studied after an overnight fast and during hyperinsulinemia using magnetic resonance spectroscopy and stable isotope tracers.
  
  
  METHODS
  IHTG, gluconeogenesis from glycerol, gluconeogenesis from the citric acid cycle, glycogenolysis, and (13)C-labeled glucose produced from the citric acid cycle during hyperinsulinemia were measured.
  
  
  RESULTS
  Men with high IHTG had higher fluxes through all pathways contributing to glucose production during hyperinsulinemia, compared to men with low IHTG, but they had similar fluxes after the fast. Consequently, men with fatty liver had impaired insulin efficiency in suppressing total glucose production as well as fluxes through all three biochemical pathways contributing to glucose. The detection of glucose isotopomers with (13)C arising from [U-(13)C3]propionate ingested during hyperinsulinemia demonstrated continuous gluconeogenesis from the citric acid cycle in all subjects.
  
  
  CONCLUSIONS
  These findings challenge the concept that individual glucose production pathways are selectively dysregulated during hepatic insulin resistance. Overproduction of glucose during hyperinsulinemia in men with fatty liver results from inadequate suppression of all the supporting fluxes of glucose production in response to insulin.
authors.affiliation: Advanced Imaging Research Center (E.S.J., J.D.Br., J.D.Ba., C.R.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-8568; Department of Internal Medicine (E.S.J., M.S.-G., J.D.B., C.R.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Department of Medicine (N.A.), Division of Endocrinology, University of Texas Medical Branch at Galveston, Texas 77555; Department of Radiology (C.R.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; and VA North Texas Health Care System (C.R.M.), Dallas, Texas 75216.
authors.forename: Eunsook S
authors.initials: ES
authors.lastname: Jin
authors.forename: Magdalene
authors.initials: M
authors.lastname: Szuszkiewicz-Garcia
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Browning
authors.forename: Jeannie D
authors.initials: JD
authors.lastname: Baxter
authors.forename: Nicola
authors.initials: N
authors.lastname: Abate
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
mesh_terms: D000328:Adult; D005234:Fatty Liver / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D007328:Insulin; D014280:Triglycerides; D005947:Glucose