Difference in sensitivity to glucagon action in three different rat liver systems.

We compared sensitivity to glucagon in three different rat liver systems. In perfused liver, half-maximal response of glycogenolysis was obtained by 5 x 10(-11) mol/L glucagon. In contrast, half-maximal response was obtained by 10(-9) mol/L glucagon in batch incubation of isolated hepatocytes. In perifusion system using the same isolated hepatocytes, 9 x 10(-11) mol/L glucagon induced half-maximal response. In both perfused liver and perifusion system, dose response relationships for glucagon-induced cyclic adenosine monophosphate (cAMP) output were identical. In batch incubation of isolated hepatocytes, again much higher concentration of glucagon was needed to increase cAMP output. Inhibitors of glucagon degradation did not increase the sensitivity of hepatocytes in batch incubation system. When the liver was perfused in recirculation system, glycogenolytic response to glucagon was significantly less than when it was perfused in flow-through system. Also, when extract of lipophilic substances in conditioned medium of batch incubation system was included in perfusate, the glycogenolytic response to glucagon was diminished in perfused liver system. In contrast to the action of glucagon, sensitivities of hepatocytes to calcium mobilizing hormones, phenylephrine, and angiotensin II, in three systems were nearly identical. These results suggest that the diminished sensitivity of hepatocytes to glucagon observed in batch incubation system is due, at least in part, to a substance (or substances) released from hepatocytes.