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1 Department of Biological Sciences, Chapman University, Orange, CA, USA
2 Department of Kinesiology, University of Southern California, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: sumida{at}chapman.edu.
The impact of reduced hepatic flow upon lactate uptake and gluconeogenesis was examined in isolated glucagon-stimulated perfused livers from 24 hour fasted rats. Following surgical isolation, livers were perfused (single-pass) for 30 min with Krebs-Henseleit (KH) 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 x 100g body weight-1). After the perfusion, the liver was dissected out and weighted so as to establish the actual flow rate per gram of liver. This resulted in a range of flow rates from 0.52 to 4.03 ml/min x 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 x 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 x g liver-1), adjustments in FX compensated for changes in lactate delivery resulting in steady rates of lactate uptake and gluconeogenesis. Below 1.0 ml/min x 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.
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