Diabetes 53:32-40, 2004 © 2004 by the American Diabetes Association, Inc. Nonesterified Fatty Acids and Hepatic Glucose Metabolism in the Conscious Dog
1 Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 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 ([3-3H]glucose), basal, and two experimental periods (-120 to -30, -30 to 0, 0120 [period 1], and 120240 min [period 2], respectively). During periods 1 and 2, somatostatin, basal intraportal insulin and glucagon, portal glucose (21.3 µmol · 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 µmol · kg-1 · min-1), respectively, endogenous glucose Ra (2.3 ± 1.4 and 10.6 ± 1.0 µmol · kg-1 · min-1), net hepatic NEFA uptakes (0.1 ± 0.1 and 1.8 ± 0.2 µmol · kg-1 · min-1), net hepatic ß-hydroxybutyrate output (0.1 ± 0.0 and 0.4 ± 0.1 µmol · kg-1 · min-1), and net hepatic lactate output (6.5 ± 1.7 vs. -2.3 ± 1.2 µmol · kg-1 · min-1). Hepatic glucose uptake and release were 2.6 µmol · kg-1 · min-1 less and 3.5 µmol · 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.
Address correspondence and reprint requests to M.C. Moore, PhD, 702 Light Hall, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615. E-mail: genie.moore{at}mcmail.vanderbilt.edu
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