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Am J Physiol Endocrinol Metab 290: E185-E191, 2006. First published August 9, 2005; doi:10.1152/ajpendo.00318.2004
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Impact of flow rate on lactate uptake and gluconeogenesis in glucagon-stimulated perfused livers

Ken D. Sumida,1 Jerry H. Urdiales,2 and Casey M. Donovan2

1Department of Biological Sciences, Chapman University, Orange, California; and 2Department of Kinesiology, University of Southern California, Los Angeles, California

Submitted 19 July 2004 ; accepted in final form 28 July 2005

The impact of reduced hepatic flow on lactate uptake and gluconeogenesis was examined in isolated glucagon-stimulated perfused livers from 24-h-fasted rats. After surgical isolation, livers were perfused (single pass) for 30 min with Krebs-Henseleit (KH) bicarbonate buffer, fresh bovine erythrocytes (hematocrit ~20%), and no added substrate. After this "washout" period, steady-state perfusions were initiated with a second reservoir containing the KH buffer, bovine erythrocytes, [U-14C]lactate (10,000 dpm/ml), lactate (2.5 mM), and glucagon (250 µg/ml). Perfusion flow rate was adjusted to one of five rates (i.e., 1.8, 2.7, 3.9, 7.4, and 11.0 ml·min–1·100 g body wt–1). After the perfusion, the liver was dissected out and weighed so as to establish the actual flow rate per gram of liver. The resulting flow rates ranged from 0.52 to 4.03 ml·min–1·g liver–1. As a function of flow rate, lactate uptake rose in a hyperbolic fashion to an apparent plateau of 2.34 µmol·min–1·g liver–1. Fractional extraction (FX) of lactate from the perfusate demonstrated an exponential decline with increased flow rates (r = 0.97). At flow rates above 1.0 ml·min–1·g liver–1, adjustments in FX compensated for changes in lactate delivery, resulting in steady rates of lactate uptake and gluconeogenesis. Below 1.0·min–1·g liver–1 the increased FX was unable to compensate for the decline in lactate delivery and lactate uptake declined rapidly. Gluconeogenesis demonstrated similar kinetics to lactate uptake, reflecting its dominant role among pathways for lactate removal under the current conditions.

fasted rats; U-14C-labeled lactate; 14C-labeled glucose


Address for reprint requests and other correspondence: K. D. Sumida, Dept. of Biological Sciences, Chapman University, One University Dr., Orange, CA 92866 (e-mail: sumida{at}chapman.edu)






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