title: Lactate delivery (not oxygen) limits hepatic gluconeogenesis when blood flow is reduced.
abstract: 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 (Vo(2)) 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), Vo(2) 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, Vo(2) 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.
authors.affiliation: Dept. of Biological Sciences, Chapman University, One Univ. Dr., Orange, CA 92866, USA. sumida@chapman.edu
authors.forename: Ken D
authors.initials: KD
authors.lastname: Sumida
authors.forename: Jerry H
authors.initials: JH
authors.lastname: Urdiales
authors.forename: Casey M
authors.initials: CM
authors.lastname: Donovan
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D005215:Fasting; D005260:Female; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000096:biosynthesis; D006003:Glycogen / Q000378:metabolism; D006400:Hematocrit; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism*; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008102:Liver Circulation / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002245:Carbon Dioxide; D019344:Lactic Acid; D006003:Glycogen; D005947:Glucose; D010100:Oxygen