Gluconeogenesis predominates in periportal regions of the liver lobule

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Abstract
1 Rates of gluconeogenesis from lactate were calculated in periportal and pericentral regions of the liver lobule in perfused rat livers from increases in O2 uptake due to lactate. When lactate (0.1–2.0 mM) was infused into livers from fasted rats perfused in either anterograde or the retrograde direction, a good correlation (r= 0.97) between rates of glucose production and extra O2 uptake by the liver was observed as expected. 2 Rates of oxygen uptake were determined subsequently in periportal and pericentral regions of the liver lobule by placing miniature oxygen electrodes on the liver surface and measuring the local change in oxygen concentration when the flow was stopped. Basal rates of oxygen uptake of 142 ± 11 and 60 ± 4 μmol × g−1× h−1 were calculated for periportal and pericentral regions, respectively. Infusion of 2 mM lactate increased oxygen uptake by 71 μmol × g−1× h−1 in periportal regions and by 29 μmol × g−1× h−1 in pericentral areas of the liver lobule. Since the stoichiometry between glucose production and extra oxygen uptake is well-established, rates of glucose production in periportal and pericentral regions of the liver lobule were calculated from local changes in rates of oxygen uptake for the first time. 3 Maximal rates of glucose production from lactate (2 mM) were 60 ± 7 and 25 ± 4 μmol × g−1× h−1 in periportal and pericentral zones of the liver lobule, respectively. The lactate concentrations required for half-maximal glucose synthesis were similar (0.4–0.5 mM) in both regions of the liver lobule in the presence or absence of epinephrine (0.1 μM). In the presence of epinephrine, maximal rates of glucose production from lactate were 79 ± 5 and 59 ± 3 μmol × g−1× h−1 in periportal and pericentral regions, respectively. Thus, gluconeogenesis from lactate predominantes in periportal areas of the liver lobule during perfusion in the anterograde direction; however, the stimulation by added epinephrine was greatest in pericentral areas. Differences in local rate? of glucose synthesis may be due to ATP availability, as a good correlation between basal rates of O2 uptake and rates of gluconeogenesis were observed in both regions of the liver lobule in the presence and absence of epinephrine. 4 In marked contrast, when livers were perfused in the retrograde direction, glucose production was 28 ± 5 μmol × g−1× h−1 in periportal areas and 74 ± 6 μmol × g−1× h−1 in pericentral regions. Epinephrine increased maximal rates of glucose production to 87 μmol × g−1× h−1 and 58 μmol × g−1× h−1 in pericentral and periportal regions, respectively. Thus, gluconeogenesis can be shifted rapidly from one region of the liver lobule to another in the hemoglobin-free perfused rat liver.