Gluconeogenesis from [l-14C]pyruvate in the perfused liver from fasted rats was stimulated by oleic acid as indicated by an increase in medium glucose, liver glycogen and specific activity of medium [14C]glucose. A balance of carbon from pyruvate revealed that in the presence of oleic acid 2 moles of pyruvate were utilized for each mole of glucose synthesized in contrast to a ratio 4: 1 without fatty acid. From this and 14C0, data it is concluded that oleic acid inhibited pyruvate oxidation markedly. Glucagon increased glucose formation from pyruvate but not from glycerol.Tremendous interest in the factors controlling the rate of gluconeogenesis has been shown in recent years. Long-chain fatty acids have been found to stimulate gluconeogenesis in the perfused rat liver using lactate [l] or alanine as substrate [2,3], and caprylate stimulates glucose formation in liver slices [4]. Increased fatty acid oxidation and ketogenesis have also been implicated in the i n vivo stimulation of gluconeogenesis by glucagon [5,6]. 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. The effect of glucagon on gluconeogenesis from glycerol and pyruvate has also been investigated.
MATERIALS AND METHODSMale albino rats (Sprague-Dawley, Gassner, Munchen), weighing between 180 and 250 g and previously fed on laboratory chow (Altromin R., Altrogge, Lage Lippe) were fasted for 18-20 h before use.All chemicals were reagent grade unless otherwise noted. L-lactic acid and DL-carnitine chloride were from Schuchardt (Munchen) and oleic acid from Riedel-DeHaen (Seelze-Hannover). The oleic acid was vacuum distilled prior to use. Glucagon was a preparation and a gift of Eli Lilly, Indianapolis, U.S.A. (Lot Nr. 258-234, B-167-1). Sodium [1-14C]-pyruvate was obtained from Radiochemical Center, Amersham, England. 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 perfusin...