title: Defective liver disposal of free fatty acids in patients with impaired glucose tolerance.
abstract: The liver exchanges high fluxes of glucose and free fatty acids (FFA) and is one main site of their reciprocal regulation. Acute exposure to hyperglycemia and hyperinsulinemia has been shown to reduce splanchnic beta-oxidation in healthy humans. We investigated whether a spontaneous condition of chronic mild hyperglycemia and hyperinsulinemia affects liver FFA uptake. Hepatic FFA influx rate constant (LKi) was measured after a 12-15-h fast in 10 patients with impaired glucose tolerance (IGT) and eight control subjects using positron emission tomography in combination with the long-chain FFA analog 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Compared with controls, IGT patients had higher serum insulin, glucose, and triglyceride levels (1.71 +/- 0.24 vs. 0.59 +/- 0.06 mmol/liter, P < 0.001), lower high-density lipoprotein (1.04 +/- 0.11 vs. 1.42 +/- 0.13 mmol/liter, P < 0.05), and similar FFA levels (0.59 +/- 0.06 vs. 0.56 +/- 0.05 mmol/liter(-1), P = not significant). LKi was significantly reduced in IGT (0.288 +/- 0.014 min(-1)) compared with control subjects (0.341 +/- 0.014 min(-1), P < 0.02). LKi was negatively correlated with plasma glucose (r = 0.51, P < 0.03), glycosylated hemoglobin (r = 0.55, P < 0.02), and blood lactate levels (r = 0.52, P < 0.03). We conclude that, in IGT patients, the ability of the liver to extract FFA from the circulation appears to be impaired. The reciprocal relationship between hepatic FFA extraction and glucose/lactate flux may derive from intrahepatic substrate competition.
authors.affiliation: Turku PET Centre, Department of Nuclear Medicine, University of Turku, FI-20521 Turku, Finland. patricia.iozzo@ifc.cnr.it
authors.forename: Patricia
authors.initials: P
authors.lastname: Iozzo
authors.forename: Anu K
authors.initials: AK
authors.lastname: Turpeinen
authors.forename: Teemu
authors.initials: T
authors.lastname: Takala
authors.forename: Vesa
authors.initials: V
authors.lastname: Oikonen
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bergman
authors.forename: Tove
authors.initials: T
authors.lastname: Grönroos
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D018149:Glucose Intolerance / Q000097:blood / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014055:Tomography, Emission-Computed
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; C071178:14-fluoro-6-thiaheptadecanoic acid