title: A dose-response elevation in hepatic glucose uptake is paralleled by liver triglyceride synthesis and release.
abstract: OBJECTIVE
  Enhanced release of triglycerides (TG) by the liver is implicated in the pathogenesis of the metabolic syndrome. The aim of the study was to evaluate whether a primary elevation in hepatic glucose utilization (HGU), as induced by an acute rise in circulating glucose values during physiological hyperinsulinemia, promotes TG synthesis in spite of the reduction in free fatty acids (FFA) levels.
  
  
  METHODS
  Glucose dose-response studies were conducted in anesthetized pigs using positron emission tomography (PET) to quantify HGU during fasting euglycemic conditions (EF), and under two-step hyperglycemic hyperinsulinemia (1st-HH +3.0, 2nd-HH +6.0 mmol/L over EF glucose values). Liver biopsies were obtained in three animals to evaluate the relationship between glucose exposure and hepatic fat content.
  
  
  RESULTS
  Plasma glucose levels were progressively increased in the two-step studies, and otherwise stable within every hour of PET scanning. HGU increased almost fivefold with raising glucose levels, from 0.033 ± 0.009 in EF to 0.149 ± 0.043 in 1st-HH, p = 0.02, and to 0.138 ± 0.050 μmol/min/g in 2nd-HH, p = 0.03. Circulating TG concentrations increased by 50 and 100% in the two hyperglycemic conditions (p = 0.03 2nd-HH vs. EF), in spite of a 70% suppression in plasma FFA levels. The hepatic TG content paralleled the glucose loads. Plasma γ-glutamyl transferase (γ-GT) was increased by 17% (p < 0.05).
  
  
  CONCLUSIONS
  A short-term elevation in circulating glucose levels within the physiological postprandial range was sufficient to increase HGU, resulting in a significant synthesis and release of TG by the liver, which was accompanied by an acute rise in γ-GT and liver fat content.
authors.affiliation: Institute of Clinical Physiology, CNR National Research Council, Pisa, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Guiducci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.forename: Silvia
authors.initials: S
authors.lastname: Burchielli
authors.forename: Claudia
authors.initials: C
authors.lastname: Simi
authors.forename: Stefano
authors.initials: S
authors.lastname: Masi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Liistro
authors.forename: Silvia
authors.initials: S
authors.lastname: Pardini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Porciello
authors.forename: Pietro
authors.initials: P
authors.lastname: Di Cecco
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.forename: Alessandra
authors.initials: A
authors.lastname: Calcagno
authors.forename: Demetrio
authors.initials: D
authors.lastname: Ciociaro
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
authors.forename: Piero A
authors.initials: PA
authors.lastname: Salvadori
authors.forename: Patricia
authors.initials: P
authors.lastname: Iozzo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006943:Hyperglycemia; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D013552:Swine; D014280:Triglycerides / Q000096:biosynthesis* / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D005723:gamma-Glutamyltransferase; D005947:Glucose