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R T Mallet

Publications and source records attributed to R T Mallet.

34 records · Page 2Linked to original sources
PubMed1993

Mitochondrial pyruvate transport in working guinea-pig heart. Work-related vs. carrier-mediated control of pyruvate oxidation.

Myocardial pyruvate oxidation is work- or calcium-load-related, but control of pyruvate dehydrogenase (PDH) by the specific mitochondrial pyruvate transporter has also been proposed. To test the transport hypothesis distribution of pyruvate across the cell membrane as well as rates of mitochondrial pyruvate net transport plus oxidation were examined in isolated perfused but stable and physiologically working guinea-pig hearts. 150 microM-1.2 mM alpha-cyanohydroxycinnamate proved to specifically block mitochondrial pyruvate uptake in these hearts. When perfusate glucose as cytosolic pyruvate precursor was supplied in combination with octanoate (0.2 or 0.5 mM) as diffusible alternative fatty acid substrate, alpha-cyanohydroxycinnamate produced up to 20- and 3-fold increases in pyruvate and lactate efflux, respectively. Cinnamates did not alter myocardial hemodynamics nor sarcolemmal pyruvate and lactate export. In contrast the tested concentrations of cinnamate produced reversible, dose-dependent decreases in 14CO2 production from [1-14C]pyruvate or [U-14C]glucose by inhibiting mitochondrial pyruvate uptake. Linear least-squares estimates of available cinnamate-sensitive total pyruvate transport potential yielded rates close to 110 mumol/min per g dry mass at S0.5 approximately 120 microM, which compared reasonably well with literature values from isolated cardiac mitochondria. This transport potential was severalfold larger than total extractable myocardial PDH activity of approximately 32 mumol/min per g dry mass at 37 degrees C. Even when cytosolic pyruvate levels were in the lower physiologic range of about 90 microM, pyruvate oxidation readily kept pace with mitochondrial respiration over a wide range of workload and inotropism. Furthermore, dichloroacetate, a selective activator of PDH, stimulated pyruvate oxidation without affecting myocardial O2 consumption, regardless of the metabolic or inotropic state of the hearts. Consequently, little or no regulatory function with regard to pyruvate oxidation could be assigned to the native mitochondrial pyruvate carrier of the working heart. Therefore, mitochondrial pyruvate-H+ symport was the normal, highly efficient (rather than controlling) mechanism for pyruvate entry into the mitochondria where PDH regulation controlled pyruvate oxidation.

Adrenergic Agonists↗
PubMed1993

Metabolic protection of post-ischemic phosphorylation potential and ventricular performance.

Relationships between cytosolic phosphorylation potential, low-flow ischemic purine release and post-ischemic left ventricular developed pressure were examined in perfused working guinea-pig heart. During moderate ischemic acidification, metabolic intervention by pyruvate attenuated cytosolic NADH accumulation and (ATP+ADP+AMP) degradation. In reperfusion, spontaneously developed ventricular pressure increased in parallel with the phosphorylation potential (R2 = 0.71), but forced restoration of function by inotropic measures occurred at the expense of the phosphorylation potential.

Adenosine Triphosphate↗
PubMed1993

Hypoxic preconditioning attenuates stunning caused by repeated coronary artery occlusions in dog heart.

OBJECTIVE: The aim was to test whether a brief period of non-ischaemic hypoxia can attenuate cardiac contractile dysfunction, ie, "stunning", due to repeated coronary artery occlusions. METHODS: 20 anaesthetised dogs underwent six 5 min occlusions of the left anterior descending coronary artery with intervening 10 min reperfusions, prior to 90 min reperfusion. In the treated group (n = 9), hearts were preconditioned by 5 min extracorporeal left anterior perfusion with severely hypoxic blood [O2 content 14(SEM 3) ml.litre-1] followed by 10 min reperfusion, prior to the repeated coronary occlusions. Controls (n = 9) were sham preconditioned by 5 min extracorporeal perfusion with normoxic blood [O2 content 179(7) ml.litre-1]. Regional contractile function was assessed by systolic segmental shortening measured by microsonometry. Regional myocardial oxygen consumption, an index of ATP utilisation, was measured in these protocols to evaluate the hypothesis that reduction of myocardial energy demand could be a mechanism of hypoxic preconditioning. RESULTS: Hypoxic preconditioning slightly decreased systolic segmental shortening [64.1(9.5)% of baseline at 10 min reoxygenation v 85.5(6.5)% for control, p < 0.05]. In contrast, 5 min coronary occlusion in controls produced more marked cardiodepression [segmental shortening 33.5(10.1)% of baseline at 10 min reperfusion; p < 0.05 v 10 min reoxygenation in the hypoxic-preconditioned group]. Systolic shortening was preserved in hypoxic-preconditioned hearts as compared to controls during each 10 min reperfusion period. Furthermore, functional recovery at 90 min reperfusion after the last occlusion in hypoxic preconditioned hearts was more complete than in control hearts, at 40.8(13.1)% v -16.1(14.4)%; p < 0.05. However, myocardial oxygen consumption was not suppressed by hypoxic preconditioning. CONCLUSIONS: Five minutes of hypoxic preconditioning attenuated contractile dysfunction due to repeated brief ischaemia/reperfusion stress. This protective effect was not due to the suppression of myocardial energy demand.

Adenosine Triphosphate↗
PubMed1992

Use of cytosolic metabolite patterns to estimate free magnesium in normoxic myocardium.

Cytosolic free magnesium (Mgf) is considered relatively constant. To test this concept, Mgf was estimated during hyperkalemic ventricular akinesis, normal and maximum adrenergic stimulation, and sulfate loading of the normoxic perfused guinea-pig heart. The Mgf estimates utilized a new sliding scale derived from the Mg(2+)-dependence of glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase (GAPDH/PGK). The pseudo constant K'GAPDH.K'PGK was measured as ([creatine phosphate][3-phosphoglycerate][lactate]KLDH)/([creatine][Pi] [glyceraldehyde 3-phosphate][pyruvate]KCK), which varied with magnesium due to KCK (CK, LDH = creatine kinase, lactate dehydrogenase). However, the correct magnesium dependencies of the true constants KGAPDH.KPGK and KCK were taken from the literature. The [Mg2+] at which pseudo K'GAPDH.K'PGK equalled true KGAPDH.KPGK was the best estimate of Mgf.Mgf fell to approximately 0.13 mM in hyperkalemic arrest from a control of approximately 0.6 mM, rising to approximately 0.85 mM only during maximum adrenergic stress. Mgf increased further to approximately 1.3 mM during sulfate loading which induced ATP catabolism. Mgf and ATP were reciprocally related. Thus; (1) myocardial free [Mg2+] judged from GADPH/PGK mass-action relations changed appreciably only under extreme physiological states; (2) ATP was a major chelator of Mg2+ in perfused myocardium, i.e., acute ATP pool size reduction may be associated with increments in Mgf.

Aconitate Hydratase↗
PubMed1992

Coronary autoregulation and purine release in normoxic heart at various cytoplasmic phosphorylation potentials: disparate effects of adenosine.

The impacts of energy-yielding substrates on coronary flow autoregulation, cytoplasmic phosphorylation potential ([ATP]/([ADP][Pi])] and purine nucleoside production were studied in Langendorff-perfused guinea pig hearts. The perfusion medium was substrate-free or contained glucose alone or in combination with pyruvate, lactate, acetate, or octanoate as fatty acid. When coronary flow was adjusted for myocardial oxygen consumption, only pyruvate supported near-perfect intrinsic autoregulation at highly sustained [ATP]/([ADP][Pi]) and low interstitial adenosine concentrations ([Ado]). In contrast, hearts perfused with substrate-free medium were deenergized at very high [Ado], especially at supraphysiological pressures, which markedly impaired auto-regulatory vasoconstriction. Thus, efficient autoregulatory vasoconstriction was associated with high [ATP]/([ADP][Pi]) at low [Ado]. On the other hand, autoregulatory vasodilation at subphysiological pressures was associated with increased [Ado] and partially blocked by 28 microM theophylline demonstrating (partial) adenosine mediation. Massive accumulation of IMP, especially relative to free cytoplasmic AMP, occurred at normal intracellular pH during myocyte deenergization by substrate-free perfusion. This may indicate allosteric activation of native AMP deaminase in situ, perhaps because of collapse of [ATP]/([ADP][Pi]). Similarly, rates of adenosine plus inosine release and of total purines, also including urate, exhibited non-linear sigmoidal rather than linear or rectangular hyperbolic dependences on free cytoplasmic AMP concentration (not total AMP content). Since inclusion of IMP as a co-variable of free AMP appreciably improved the sigmoidal fits, IMP appeared to be a significant precursor of released inosine in guinea pig heart.

Adenosine↗
PubMed1992

Hypoxic preconditioning of ischaemic canine myocardium.

OBJECTIVE: The aim was to test whether a brief period of non-ischaemic hypoxia can precondition myocardium. METHODS: 60 anaesthetised adult mongrel dogs of either sex underwent 60 min occlusion of the left anterior descending coronary artery, followed by 5 h reperfusion. In treated groups, hearts were either preconditioned with 5 min coronary perfusion with hypoxic blood [O2 content 9.2(SEM 0.6) ml.litre-1] or 5 min occlusion followed by a 10 min reperfusion period prior to 60 min occlusion. The effect of these treatments on myocardial infarct size and regional contractile function was assessed. RESULTS: Infarct size, determined by tetrazolium staining, as a percentage of anatomical area at risk was markedly decreased in hypoxia preconditioned hearts, at 7.2(1.8)% v 22.4(4.6)% in controls (p < 0.01), but did not differ from ischaemia preconditioned hearts [4.6(1.7)%; p < 0.01 v control]. Anatomical area at risk, expressed as a percentage of left ventricular mass, and collateral blood flow to the inner two thirds of the ischaemic wall did not differ among the groups. Regional contractile function was depressed following ischaemic preconditioning but not following hypoxic preconditioning. During reperfusion following 60 min occlusion, marked paradoxical systolic lengthening was evident in ischaemia preconditioned and control hearts but not in hypoxia preconditioned myocardium. CONCLUSIONS: Five minutes of hypoxic and ischaemic preconditioning were equipotent in preventing infarction, whereas ischaemic preconditioning caused a greater decrement in postischaemic contractile function.

Animals↗
PubMed1992

Canine coronary vasodepressor responses to hypoxia are attenuated but not abolished by 8-phenyltheophylline.

The purpose of this study was twofold: 1) to verify a report that a suspension of 8-phenyltheophylline (8-PT) completely abolished hypoxia-induced coronary vasodilation [H. M. Wei, Y. H. Kang, and G. F. Merrill. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1043-H1048, 1989] and 2) to determine the effect of dissolved 8-PT on hypoxic hyperemia. The left anterior descending coronary artery of anesthetized dogs was cannulated and perfused at either constant flow or constant pressure. An 8-PT suspension (40 micrograms.kg-1.min-1) produced a twofold elevation of coronary perfusion pressure at constant flow, a 97% decrease in coronary flow at constant pressure, and regional akinesia in both conditions. The coronary vasculature was unresponsive to 60-s coronary occlusion, exogenous adenosine, and hypoxia after infusion of the 8-PT suspension. These findings are consistent with obstruction of the coronary microvasculature by the 8-PT suspension. An 8-PT solution (40 micrograms.kg-1.min-1) produced 95 +/- 3% (P less than 0.001, n = 6) attenuation of exogenous adenosine-induced vasodilation at constant pressure, a 28 +/- 5% (P less than 0.01, n = 6) attenuation of reactive hyperemia, and a 24 +/- 6% (P less than 0.05, n = 6) decrease in hypoxia-induced vasodilation. An 8-PT solution had no effect on systolic segment length shortening and myocardial oxygen consumption. We conclude that 8-PT, when in solution, attenuates but does not abolish the coronary vasodilatory response to hypoxia. Hence, adenosine appears to contribute to hypoxia-induced vasodilation but is not uniquely responsible for the hyperemic response.

Adenosine↗
PubMed1991

Combined glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase in catecholamine-stimulated guinea-pig cardiac muscle. Comparison with mass-action ratio of creatine kinase.

The steady-state reactant levels of triose-phosphate isomerase and the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase system were examined in guinea-pig cardiac muscle. Key glycolytic intermediates, including glyceraldehyde 3-phosphate were directly measured and compared with those of creatine kinase. Non-working Langendorff hearts as well as isolated working hearts were perfused with 5 mM glucose (plus insulin) under normoxia conditions to maintain lactate dehydrogenase near-equilibrium. The cytosolic phosphorylation potential ([ATP]/([ADP].[Pi])) was derived from creatine kinase and the free [NAD+]/([NADH].[H+]) ratio from lactate dehydrogenase. In Langendorff hearts glycolysis was varied from near-zero flux (hyperkalemic cardiac arrest) to higher than normal flux (normal and maximum catecholamine stimulation). The triose-phosphate isomerase was near-equilibrium only in control or potassium-arrested Langendorff hearts as well as in postischemic 'stunned' hearts. However, when glycolytic flux increased due to norepinephrine or due to physiological pressure-volume work the enzyme was displaced from equilibrium. The alternative phosphorylation ratio [ATP]'/([ADP]).[Pi]) was derived from the magnesium-dependent glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase system assigning free magnesium different values in the physiological range (0.1-2.0 mM). As predicted, [ATP]/([ADP].[Pi]) and [ATP]'/([ADP]'.[Pi]') were in excellent agreement when glycolysis was virtually halted by hyperkalemic arrest (flux approximately 0.2 mumol C3.min-1.g dry mass-1). However, the equality between the two phosphorylation ratios was not abolished upon resumption of spontaneous beating and also not during adrenergic stimulation (flux approximately 5-14 mumol C3.min-1.g dry mass-1). In contrast, when flux increased due to transition from no-work to physiological pressure-volume work (rate increase from approximately 3 to 11 mumol C3.min-1.g dry mass-1), the two ratios were markedly different indicating disequilibrium of the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase. Only during adrenergic stimulation or postischemic myocardial 'stunning', not due to hydraulic work load per se, glyceraldehyde-3-phosphate levels increased from about 4 microM to greater than or equal to 16 microM. Thus the guinea-pig cardiac glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase system can realize the potential for near-equilibrium catalysis at significant flux provided glyceraldehyde-3-phosphate levels rise, e.g., due to 'stunning' or adrenergic hormones.

Animals↗
PubMed1990

Glucose requirement for postischemic recovery of perfused working heart.

The quantitative importance of glycolysis in cardiomyocyte reenergization and contractile recovery was examined in postischemic, preload-controlled, isolated working guinea pig hearts. A 25-min global but low-flow ischemia with concurrent norepinephrine infusion to exhaust cellular glycogen stores was followed by a 15-min reperfusion. With 5 mM pyruvate as sole reperfusion substrate, severe contractile failure developed despite normal sarcolemmal pyruvate transport rate and high intracellular pyruvate concentrations near 2 mM. Reperfusion dysfunction was characterized by a low cytosolic phosphorylation potential [( ATP]/[( ADP][Pi]) due to accumulations of inorganic phosphate (Pi) and lactate. In contrast, with 5 mM glucose plus pyruvate as substrates, but not with glucose as sole substrate, reperfusion phosphorylation potential and function recovered to near normal. During the critical ischemia-reperfusion transition at 30 s reperfusion the cytosolic creatine kinase appeared displaced from equilibrium, regardless of the substrate supply. When under these conditions glucose and pyruvate were coinfused, glycolytic flux was near maximum, the glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase reaction was enhanced, accumulation of Pi was attenuated, ATP content was slightly increased, and adenosine release was low. Thus, glucose prevented deterioration of the phosphorylation potential to levels incompatible with reperfusion recovery. Immediate energetic support due to maximum glycolytic ATP production and enhancement of the glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase reaction appeared to act in concert to prevent detrimental collapse of [ATP]/[( ADP][Pi]) during creatine kinase dysfunction in the ischemia-reperfusion transition. Dichloroacetate (2 mM) plus glucose stimulated glycolysis but failed fully to reenergize the reperfused heart; conversely, 10 mM 2-deoxyglucose plus pyruvate inhibited glycolysis and produced virtually instantaneous de-energization during reperfusion. The following conclusions were reached. (1) A functional glycolysis is required to prevent energetic and contractile collapse of the low-flow ischemic or reperfused heart (2). Glucose stabilization of energetics in pyruvate-perfused hearts is due in part to intensification of glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase activity. (3) 2-Deoxyglucose depletes the glyceraldehyde-3-phosphate pool and effects intracellular phosphate fixation in the form of 2-deoxyglucose 6-phosphate, but the cytosolic phosphorylation potential is not increased and reperfusion failure occurs instantly. (4) Consistent correlations exist between cytosolic ATP phosphorylation potential and reperfusion contractile function. The findings depict glycolysis as a highly adaptive emergency mechanism which can prevent deleterious myocyte deenergization during forced ischemia-reperfusion transitions in presence of excess oxidative substrate.

Animals↗
PubMed1989

Pyruvate-enhanced phosphorylation potential and inotropism in normoxic and postischemic isolated working heart. Near-complete prevention of reperfusion contractile failure.

Bioenergetic and hemodynamic consequences of cellular redox manipulations by 0.2-20 mM pyruvate were compared with those due to adrenergic stress (0.7-1.1 microM norepinephrine) using isolated working guinea-pig hearts under the conditions of normoxia, low-flow ischemia, and reperfusion. 5 mM glucose (+ 5 U/l insulin) + 5 mM lactate were the basal energy-yielding substrates. To stabilize left ventricular enddiastolic pressure, ventricular filling pressure was held at 12 cmH2O under all conditions; this preload control minimized Frank-Starling effects on ventricular inotropism. Global low-flow ischemia was induced by reducing aortic pressure to levels (20-10 cmH2O) below the coronary autoregulatory reserve. Reactants of the creatine kinase, including H+ and other key metabolites, were measured by enzymatic, HPLC, and polarographic techniques. In normoxic hearts, norepinephrine stimulations of inotropism, heart rate x pressure product, and oxygen consumption (MVO2) were associated with a fall in the cytosolic phosphorylation potential [( ATP]/[( ADP].[Pi]] as judged by the creatine kinase equilibrium. In contrast, infusion of excess pyruvate (5 mM) markedly increased [ATP]/[( ADP].[Pi]) and ventricular work output, while intracellular phosphate decreased; MVO2 remained constant under the same conditions. During reperfusion following ischemia, pyruvate effected striking and concentration-dependent increases in MVO2, phosphorylation potential, and inotropism. Pyruvate dehydrogenase flux was augmented during reperfusion hyperemia followed by near-complete recoveries of [ATP]/([ADP].[Pi]), contractile force, heart rate x pressure product, and MVO2 in the presence of 5-10 mM pyruvate. Pyruvate also attenuated ischemic adenylate degradation. Omission of glucose from the perfusion medium rendered pyruvate ineffective in postischemic hearts. Similarly, excess lactate (5-15 mM) or acetate (5 mM) failed to reenergize reperfused hearts and severe depressions of MVO2 and inotropism developed despite the presence of glucose. Apparently, subcellular redox manipulations by pyruvate dissociated stimulated mitochondrial respiration and increased inotropism from low cytosolic phosphorylation potentials. This was evidence against the extramitochondrial [ADP].[Pi]/[ATP] ratio being the primary factor in the control of mitochondrial respiration. The mechanism of pyruvate enhancement of inotropism during normoxia and reperfusion is probably multifactorial. Thermodynamic effects on subcellular [NADH]/[NAD+] ratios are coupled with a rise in the cytosolic [ATP]/[( ADP].[Pi]) ratio at constant (normoxia) or increased (reperfusion) MVO2.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗
PubMed1988

Effect of Na+ on intestinal succinate transport and metabolism in vitro.

The effect of Na+ on 14CO2 production from [14C]succinate was studied in isolated rat enterocytes, and Na+-dependent succinate transport was characterized in pig intestinal brush-border membrane vesicles. The production of 14CO2 from [14C]succinate by enterocytes was decreased 12-fold when Na+ was replaced by N-methyl-D-glucamine in the absence of glutamine and 20-fold in the presence of 0.2 or 0.5 mM glutamine. The ratio of 14CO2 produced from [1,4-14C]succinate to that produced by [2,3-14C]succinate was not affected by Na+ replacement, indicating that the pattern of tricarboxylic acid cycle metabolism was not altered. The uptake of [14C]succinate by brush-border membrane vesicles was stimulated 10-fold in the presence of 100 mM NaCl compared with 100 mM KCl. When succinate uptake was corrected to transport into an osmotically sensitive space, the magnitude of the Na+ stimulation was 20-fold. Succinate transport into brush-border membrane vesicles was Na+ dependent, electroneutral, nonconcentrative, with an apparent Na+-succinate coupling ratio of 2:1. Results of this study indicate that Na+-stimulated CO2 production by enterocytes can be explained by the effect of Na+ on succinate transport across the brush-border membrane.

Amiloride↗
PubMed1987

Analysis of tricarboxylic acid-cycle metabolism of hepatoma cells by comparison of 14CO2 ratios.

The CO2-ratios method is applied to the analysis of abnormalities of TCA (tricarboxylic acid)-cycle metabolism in AS-30D rat ascites-hepatoma cells. This method utilizes steady-state 14CO2-production rates from pairs of tracers of the same compound to evaluate TCA-cycle flux patterns. Equations are presented that quantitatively convert CO2 ratios into estimates of probability of flux through TCA-cycle-related pathways. Results of this study indicated that the ratio of 14CO2 produced from [1,4-14C]succinate to 14CO2 produced from [2,3-14C]succinate was increased by the addition of glutamine (5 mM) to the medium. An increase in the succinate CO2 ratio is quantitatively related to an increased flux of unlabelled carbon into the TCA-cycle-intermediate pools. Analysis of 14C distribution in [14C]citrate derived from [2,3-14C]succinate indicated that flux from the TCA cycle to the acetyl-CoA-derived carbons of citrate was insignificant. Thus the increased succinate CO2 ratio observed in the presence of glutamine could only result from an increased flux of carbon into the span of the TCA cycle from citrate to oxaloacetate. This result is consistent with increased flux of glutamine to alpha-oxoglutarate in the incubation medium containing exogenous glutamine. Comparison of the pyruvate CO2 ratio, steady-state 14CO2 production from [2-14C]pyruvate versus [3-14C]pyruvate, with the succinate 14CO2 ratio detected flux of pyruvate to C4 TCA-cycle intermediates in the medium containing glutamine. This result was consistent with the observation that [14C]aspartate derived from [2-14C]pyruvate was labelled in C-2 and C-3. 14C analysis also produced evidence for flux of TCA-cycle carbon to alanine. This study demonstrates that the CO2-ratios method is applicable in the analysis of the metabolic properties of AS-30D cells. This methodology has verified that the atypical TCA-cycle metabolism previously described for AS-30D-cell mitochondria occurs in intact AS-30D rat hepatoma cells.

Animals↗
PubMed1986

Substrate metabolism of isolated jejunal epithelium: conservation of three-carbon units.

This study characterizes the substrate metabolism of isolated jejunal epithelial cells. Utilization of substrates was assessed by spectrophotometric assay. Significant quantities of glucose, glutamine, and ketone bodies were consumed in a 1-h period; lactate and ammonia were produced. [U-14C]glucose was metabolized in this medium to approximately three moles of lactate per mole of CO2. The pattern of tricarboxylic acid (TCA) cycle metabolism was analyzed utilizing media containing different concentrations of potential metabolic substrates and trace quantities of [14C]- succinate. O2 consumption rates indicated that glutamine can serve as an energy source in the absence of other substrates. Relative 14CO2 production from [1,4-14C]succinate versus [2,3-14C]succinate, which estimates flux of TCA cycle intermediates to products other than CO2, was increased more than twofold when glutamine was the only major substrate available. Alanine was produced from TCA cycle intermediates. Analysis of the citrate labeling pattern in the presence of [2,3-14C] succinate suggested that carbon from the TCA cycle does not form a significant fraction of acetyl-CoA used for citrate synthesis and that glutamine carbon was not completely oxidized to CO2. These findings suggest that glucose and glutamine are converted to three-carbon compounds by the jejunal epithelium.

Animals↗
PubMed1986

Jejunal epithelial glucose metabolism: effects of Na+ replacement.

The objective of this study was to characterize the effects of replacement of extracellular Na+ with a nontransportable cation, N-methyl-D-glucamine (NMDG+) on jejunal epithelial glucose metabolism. Jejunal epithelium isolated from male Sprague-Dawley rats was incubated in media containing 5 mM glucose, 0.5 mM glutamine, 0.5 mM beta-hydroxybutyrate, and 0.3 mM acetoacetate as the principal carbon sources. O2 consumption and total glucose utilization were reduced 30 and 50%, respectively, when Na+ was replaced with NMDG+. In both media, approximately 75% of utilized glucose carbon was converted to lactate. The rate of glucose metabolism via the hexose monophosphate shunt, as evaluated using specific 14CO2 yields from [1-14C]glucose and [6-14C]glucose, was not appreciably altered by Na+ replacement. Tricarboxylic acid (TCA) cycle flux was evaluated using 14CO2 production from [14C]glucose and [14C]pyruvate radioisotopes. Approximately 50% of TCA cycle flux was shunted into products other than CO2 in both media. The majority of the acetyl-CoA oxidized in the TCA cycle was derived from cytosolic pyruvate. It is concluded that removal of Na+ from the bathing medium substantially reduced glucose utilization via the Embden-Meyerhof pathway and TCA cycle in the jejunal epithelium.

Animals↗
PubMedDate not supplied

Local glucose utilization and local blood flow in hearts of awake rats.

Local cardiac glucose utilization and local cardiac blood flow in rat heart were measured in vivo by quantitative autoradiographic techniques with 2-[14C] deoxyglucose and [14C] iodoantipyrine, respectively. [14C]methylmethacrylate standards were calibrated for quantitative autoradiography of dried sections of heart tissue; the calibration values for heart tissue differed from those for brain by 8%, probably because of differences in self-absorption within the tissues. The lumped constant required by the deoxyglucose method was determined in isolated, perfused, working rat hearts and found to be 1.11 +/- 0.36 (mean +/- SD, n = 21). The heart: blood partition coefficient for iodoantipyrine required by the [14C]iodoantipyrine method was measured and found to be 1.25. The results obtained in awake rats showed: 1) overall cardiac glucose utilization varied considerably among animals with a mean of 53 (left ventricle) and 30 (right ventricle) mumol/100 g/min; 2) cardiac blood flow was less variable among animals with a mean of 592 (left ventricle) and 420 (right ventricle) ml/100 g/min; 3) glucose utilization was found to be particularly high in the papillary muscle; 4) systematic gradients of glucose utilization or blood flow in the ventricular wall were not observed; 5) glucose utilization and blood flow were not closely correlated on a local level. It is concluded that autoradiographic methods are suitable for the quantification of local glucose utilization and local blood flow in the rat heart in vivo. These methods could not demonstrate transmural gradients for glucose utilization and blood flow between epi- and endocardium in awake rats.

Animals↗