Glucagon Actions in Perfused Liver are Oxygen Dependent

Abstract

It is well known that glucagon stimulates O2 uptake in livers from fed rats, in part due to inhibition of glycolysis. An effect of glucagon on O2 uptake of isolated mitochondria following treatment of rats with glucagon has also been observed in many studies; however, its existence remains controversial. In these studies, livers from well fed female Sprague-Dawley rats (100–150 g) were perfused at flow rates of 4 or 8 ml/g/min to deliver oxygen to the liver at various rates. During perfusion at normal flow rates (4 ml/g/min), glucagon (10 nM) increased oxygen uptake by about 40 μmol/g/h. In sharp contrast, glucagon increased O2 uptake by nearly 100 μmol/g/h during perfusion at high flow rates. This increase was not due to increased glucagon delivery since infusion of 120 nM glucagon at normal flow rates only elevated oxygen uptake by 40 μmol/g/h. Glucagon also increased O2 uptake to a greater extent (2-fold) at high versus low O2 when O2 tension was manipulated by perfusing with buffers containing various O2 concentrations at constant flow rates suggesting dependence of the glucagon effect on O2 concentration. Bromocyclic AMP (25 μM) also increased O2 uptake about 2-fold more at high compared to normal flow rates. In contrast, O2 uptake was not increased more at high flow rates when intracellular Ca was elevated by infusion of angiotensin II (5 nM).