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Am J Physiol Endocrinol Metab 290: E192-E198, 2006. First published September 6, 2005; doi:10.1152/ajpendo.00319.2004
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Lactate delivery (not oxygen) limits hepatic gluconeogenesis when blood flow is reduced

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

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

Submitted 19 July 2004 ; accepted in final form 31 August 2005

The purpose of this study was to determine, using the isolated liver perfusion technique, whether the limiting factor for hepatic gluconeogenesis (GNG) from lactate was precursor delivery or oxygen availability during reduced flow rates of 0.85 or 0.60 ml·min–1·g liver–1. After a 24-h fast, three different experimental protocols were employed. Protocol 1 examined the impact on GNG when reservoir lactate concentration was maintained but oxygen delivery was elevated via increases in hematocrit (Hct). Elevating the Hct from 22.5 ± 0.8% to 30.9 ± 0.4% at a blood flow of 0.89 ± 0.01 ml·min–1·g liver–1 increased the oxygen consumption (VO2) but did not augment GNG. Similarly, when the Hct was elevated from 22.5 ± 0.8% to 41.5 ± 0.7% at 0.59 ± 0.04 ml·min–1·g liver–1, VO2 was increased, but GNG was unaffected. Protocol 2 examined the impact on GNG when Hct was maintained but precursor delivery was elevated via increases in reservoir lactate concentration ([LA]). Specifically, elevating the [LA] from 2.31 ± 0.07 to 3.61 ± 0.33 mM at a flow rate of 0.82 ± 0.04 ml·min–1·g liver–1 significantly increased GNG. Similarly, elevating the [LA] from 2.31 ± 0.07 to 4.24 ± 0.37 mM at a flow rate of 0.58 ± 0.02 ml·min–1·g liver–1 increased GNG. Finally, we examined the impact of increasing both the oxygen and lactate delivery (Protocol 3). Again, VO2 was elevated with increased oxygen delivery, but GNG was not augmented beyond that observed with elevations in lactate delivery alone, i.e., Protocol 2. The results indicate that, during decrements in blood flow, GNG is limited primarily by precursor delivery, not oxygen availability.

liver perfusion; hematocrit; 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 Univ. Dr., Orange, CA 92866 (e-mail: sumida{at}chapman.edu)







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