Differential Effects of Glucagon on Induction of Rat Liver GIucose-6-Phosphate Dehydrogenase by Liver Injury and Dietary Change

Abstract

Glucagon effectively prevented the increase in glucose-6-phosphate dehydrogenase activity of rat liver following the administration of a glucose-casein mixture without altering the amount of the diet consumed. However, the increase of the enzyme level in carbon tetrachloride-injured rat liver was virtually insensitive to glucagon. The results obtained gave further evidence for the difference between these two induction mechanisms of glucose-6-phosphate dehydrogenase.

Prevention of Dietary Induction of Rat Liver Glucose-6-Phosphate Dehydrogenase by Cyclic Adenosine 3', 5'-Monophosphate and Its Elimination by Glucose Prefeeding

“…These results suggest the importance of cyclic AMP concentration in liver in the dietary regulation of hepatic G6PD as discussed in our separate paper [42],…”

“…Even though insulin is the inducer of G6PD, its action may not be mediated by cyclic AMP, because insulin seems to be ineffective in lowering the basal level of cyclic AMP [15,19]. However, under the condition of glucagon stimulation of the adenylate cyclase system, insulin would play a role in inducing G6PD by decreasing the level of hepatic cyclic AMP [1], In contrast to the dietary induction of G6PD, the enzyme induction by CCl4-mediated liver injury was shown to be essentially insensitive to glucagon [42], This is consistent with the fact reported by us that the induction of liver G6PD by CC14 hepatic injury is due to an altered mechanism of posttranscriptional regulation of the enzyme synthesis [39], The results obtained in the present study gave a further evidence for the different mechanisms of G6PD induction by nutritional alteration and liver injury.…”

“…Preparations of liver supernatants and assays of G6PD, pyruvate kinase (EC 2.7.1.40) and glucokinase (EC 2.7.1.2) activities were carried out as described in our previous paper [42]. The relative activities of pyruvate kinase type L were determined by differential inhibition by adenosine 5'-triphosphate [33].…”

Suppressed Dietary Inducibility of Glucose 6-Phosphate Dehydrogenase and Elevated Cyclic AMP in Acute Hepatic Injury

“…Thus, the dehydrogenase level in rat liver is under a dual dietary control, i. e. transcriptional and posttranscriptional regulations; a glucose-dependent step of the induction being sensitive to actinomycin D (3) and blocked by increasing cyclic 3',5'-adenosine monophosphate (cyclic AMP) level (4). An entirely different type of G6PD induction could be brought about by intoxication of rat with carbon tetrachloride and other hepatotoxins (5)(6)(7).…”

“…An entirely different type of G6PD induction could be brought about by intoxication of rat with carbon tetrachloride and other hepatotoxins (5)(6)(7). Although the synthesis de novo of the enzyme protein is involved in the hepatotoxin-induced increase in G6PD activity, it does not require newly synthesized RNA (5) and is insensitive to manipulations to raise hepatic cyclic AMP level (8). We found in our preliminary experiments with acute thioacetamide intoxication of rat that the dietary induction of G6PD was markedly depressed in the injured liver (9).…”