RT Journal Article SR Electronic T1 Nonesterified Fatty Acids and Hepatic Glucose Metabolism in the Conscious Dog JF Diabetes JO Diabetes FD American Diabetes Association SP 32 OP 40 DO 10.2337/diabetes.53.1.32 VO 53 IS 1 A1 Moore, Mary Courtney A1 Satake, Shosuke A1 Lautz, Margaret A1 Soleimanpour, Scott A. A1 Neal, Doss W. A1 Smith, Marta A1 Cherrington, Alan D. YR 2004 UL http://diabetes.diabetesjournals.org/content/53/1/32.abstract AB 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, 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 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 β-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.