title: Nonesterified fatty acids and hepatic glucose metabolism in the conscious dog.
abstract: We used tracer and arteriovenous difference techniques in conscious dogs to determine the effect of nonesterified fatty acids (NEFAs) on net hepatic glucose uptake (NHGU). The protocol included equilibration ([3-(3)H]glucose), basal, and two experimental periods (-120 to -30, -30 to 0, 0-120 [period 1], and 120-240 min [period 2], respectively). During periods 1 and 2, somatostatin, basal intraportal insulin and glucagon, portal glucose (21.3 micromol.kg(-1).min(-1)), peripheral glucose (to double the hepatic glucose load), and peripheral nicotinic acid (1.5 mg.kg(-1).min(-1)) were infused. During period 2, saline (nicotinic acid [NA], n = 7), lipid emulsion (NA plus lipid emulsion [NAL], n = 8), or glycerol (NA plus glycerol [NAG], n = 3) was infused peripherally. During period 2, the NA and NAL groups differed (P < 0.05) in rates of NHGU (10.5 +/- 2.08 and 4.7 +/- 1.9 micromol.g(-1).min(-1)), respectively, endogenous glucose R(a) (2.3 +/- 1.4 and 10.6 +/- 1.0 micromol.kg(-1).min(-1)), net hepatic NEFA uptakes (0.1 +/- 0.1 and 1.8 +/- 0.2 micromol.kg(-1).min(-1)), net hepatic beta-hydroxybutyrate output (0.1 +/- 0.0 and 0.4 +/- 0.1 micromol.kg(-1).min(-1)), and net hepatic lactate output (6.5 +/- 1.7 vs. -2.3 +/- 1.2 micromol.kg(-1).min(-1)). Hepatic glucose uptake and release were 2.6 micro mol. kg(-1). min(-1) less and 3.5 micro mol. kg(-1). min(-1) greater, respectively, in the NAL than NA group (NS). The NAG group did not differ significantly from the NA group in any of the parameters listed above. In the presence of hyperglycemia and relative insulin deficiency, elevated NEFAs reduce NHGU by stimulating hepatic glucose release and suppressing hepatic glucose uptake.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA. genie.moore@mcmail.vanderbilt.edu
authors.forename: Mary Courtney
authors.initials: MC
authors.lastname: Moore
authors.forename: Shosuke
authors.initials: S
authors.lastname: Satake
authors.forename: Margaret
authors.initials: M
authors.lastname: Lautz
authors.forename: Scott A
authors.initials: SA
authors.lastname: Soleimanpour
authors.forename: Doss W
authors.initials: DW
authors.lastname: Neal
authors.forename: Marta
authors.initials: M
authors.lastname: Smith
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008102:Liver Circulation / Q000502:physiology; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D023421:Models, Animal
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008112:Liver Glycogen; D006493:Heparin; D005934:Glucagon; D005947:Glucose