Pyruvatcarboxylase-Aktivität und Glucoseneubildung in der isoliert perfundierten Rattenleber

Abstract

Bei Studien zum Mechanismus der Gluconeogenese wurde in Übereinstimmung mit anderen Autoren [25, 40] eine Erhöhung der Pyruvatcarboxylase-Aktivität der Leber und Niere alloxandiabetischer Ratten beobachtet. Nach Glucocorticoidgaben konnten wir dagegen keine Aktivitätszunahme des Enzyms der Rattenleber beobachten. Glucagon bewirkte eine deutliche Steigerung der Gluconeogenese aus Laktat in der isolierten Rattenleber. Dieser Effekt war nicht von einer Aktivitätszunahme der Pyruvatcarboxylase begleitet. Die Dissoziation von Gluconeogenese und Pyruvatcarboxylase-Aktivität läßt andere Mechanismen als die einer hormonellen Enzyminduktion für die Regulation der Gluconeogenese primär bedeutungsvoll erscheinen. Eine Modifikation der Isotopenmethode zur Bestimmung der Pyruvatcarboxylase [nach 16] in tierischen Geweben wird angegeben.

Effect of Oleic Acid on the Oxidation and Gluconeogenesis from [1‐14C]Pyruvate in the Perfused Rat Liver

“…The sodium [1J4C]-pyruvate was prepared as previously described [17]. After I h of pyruvate infusion, a dose of 110 pmoles of oleic acid emulsion and 0.1 mmole uL-carnitine chloride was given.…”

“…This interrelationship between increased fatty acid oxidation and gluconeogenesis has pointed to an acetyl-CoA activation of pyruvic carboxylase [7] as one of the possible control points in gluconeogenesis [S]. Recently, caprylate [9] and palmitate [lo] have been observed to decrease the oxidation of pyruvate by rat liver mitochondria, which is possibly due to an inhibition of pyruvic dehydrogenase by acetylCoA [10,11].Although glucagon has been reported to stimulate glucose production from lactate [1,12,13], pyruvate [13], fructose [13], and glycerol [14], studies of hepatic intermediates [6,12] have indicated that glucagon may accelerate gluconeogenesis a t the ratelimiting level which exists between pyruvate and phosphoenolpyruvate.The present work is a continuation and extension of the studies on the control of gluconeogenesis initiated by Struck and co-workers in our laborato-' Y [151.These workers found a stimulation of gluconeogenesis from lactate by either glucagon or oleic acid. The present studies are concerned with gluconeogenesis from pyruvate and the effect of oleic acid on this rate.…”

“…All substrates were prepared as neutral solutions. Glucagon was dissolved in 1/250 N HCI.The apparatus and technique of perfusion were similar to that previously described [16,17]. The perfusing medium consisted of a 40ml suspension of washed human erythrocytes diluted to a final volume of 100ml with Tyrodes solution, with the final mixture containing 2 g of bovine serum albumin (Behring) and 50 mg of glucose per 100 ml[l8].…”

“…Although glucagon has been reported to stimulate glucose production from lactate [1,12,13], pyruvate [13], fructose [13], and glycerol [14], studies of hepatic intermediates [6,12] have indicated that glucagon may accelerate gluconeogenesis a t the ratelimiting level which exists between pyruvate and phosphoenolpyruvate.…”

Suppression of Pyruvate Oxidation in Liver Mitochondria in the Presence of Long‐Chain Fatty Acid

“…Since fatty acids are known to stimulate the rate of gluconeogenesis in the perfused liver [3,4], the effect of long-chain fatty acid on pyruvate oxidation in liver mitochondria has been investigated. In the incubation system described by Walter et al [I] for the study of pyruvate carboxylation in liver mitochondria, pyruvate utilisation was distributed about equally between the decarboxylation and the carboxylation reaction.…”