Description:
<jats:p>Primary cultures of adult rat hepatocytes were kept for 46 h with either insulin (‘insulin cells’) or glucagon (‘glucagon cells’) as the dominant hormone under different oxygen concentrations with 13% (v/v) O<jats:sub>2</jats:sub> mimicking arterial and 4% hepatovenous levels. Thereafter metabolic rates were measured for a 2 h period under the same (‘overall long‐term O<jats:sub>2</jats:sub> effects’) or a different (‘short‐term O<jats:sub>2</jats:sub> effects’) oxygen concentration. From the differences of the two effects the ‘intrinsic long‐term O<jats:sub>2</jats:sub> effects’ were derived.</jats:p><jats:p>Glycolysis, as measured in ‘insulin‐cells’, was stimulated by low O<jats:sub>2</jats:sub> levels. It was about threefold faster in cells cultured and tested under 4% O<jats:sub>2</jats:sub> as compared to cells cultured and tested under 13% O<jats:sub>2</jats:sub>, indicating the overall long‐term effect. Glycolysis was about twofold faster in cells cultured and tested under 4% O<jats:sub>2</jats:sub> as compared to cells cultured under 4% O<jats:sub>2</jats:sub> but tested under 13% O<jats:sub>2</jats:sub>, demonstrating the short‐term effect. Glycolysis was about 1.5‐fold faster in cells cultured and tested under 4% O<jats:sub>2</jats:sub> as compared to cells cultured under 13% O<jats:sub>2</jats:sub> but tested under 4% O<jats:sub>2</jats:sub>, showing the intrinsic long‐term effect. This difference was roughly parallel to the difference in levels of glucokinase and pyruvate kinase</jats:p><jats:p>Gluconeogenesis, as measured in ‘glucagon cells’, was stimulated by high O<jats:sub>2</jats:sub> levels. Similar to glycolysis overall long‐term, short‐term and intrinsic long‐term effects could be distinguished. The intrinsic long‐term effects determined under 13% O<jats:sub>2</jats:sub> corresponded to a 1.5‐fold stimulation and paralleled the difference in phospho<jats:italic>enol</jats:italic>pyruvate carboxykinase levels.</jats:p><jats:p>The present results show that physiological oxygen concentrations also modulate hepatic carbohydrate metabolism by long‐term effects and that the O<jats:sub>2</jats:sub> gradient over the liver parenchyma thus contributes to the metabolic differences between periportal and perivenous hepatocytes <jats:italic>in vivo</jats:italic>.</jats:p>