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Biomedical subjects

T G Redgrave

Publications and source records attributed to T G Redgrave.

At least 73 records · Page 4Linked to original sources

The effect of monostearoylglycerol on the metabolism of chylomicron-like lipid emulsions injected intravenously in rats.

In rats, remnant particles derived from chylomicron-like emulsions containing 1,3-dioleoyl-2-stearoylglycerol (OSO) are removed from plasma more slowly than remnants derived from triolein emulsions. The effect associated with a saturated acyl chain at the glycerol 2-position could be reproduced by incorporating 2-stearoylglycerol (MS) in a triolein emulsion. When MS solubilized with rat albumin or in plasma was injected before the injection of a triolein emulsion, clearance of the triolein emulsion was unchanged. The metabolic fate of MS, monitored with 14C-labelled MS, was similar whether incorporated in triacylglycerol emulsion or injected independently. More than 95% of MS had disappeared from the circulation by 5 min after the injection and the radioactivity was found in liver, spleen, muscle and adipose tissue. Some MS label appeared in plasma triacylglycerol. Remnants made in vitro by incubating triolein or OSO emulsions with post-heparin plasma showed no differences in their disappearance from plasma. With OSO emulsion, the in vitro remnants were found to contain more MS than remnants made in vivo in hepatectomized rats. Simultaneous injections of mixtures containing OSO and triolein emulsions, or triolein emulsions with and without MS, each labelled with either [3H]cholesteryl oleate or [14C]cholesteryl oleate showed consistently slower remnant removal and decreased liver uptake of the emulsions containing OSO or MS. Affinity columns and immunodiffusion all indicated that there was no difference in the amounts of apolipoprotein E associated with OSO or triolein particles. The protein spectra of in vivo remnants derived from OSO and triolein emulsion were also similar when examined by SDS-PAGE and isoelectric focusing gels. Our results show that the effects due to OSO or MS are mediated by the presence of MS in the emulsion particle surface, while indirect effects expressed in plasma or liver are excluded. The precise mechanism of the effect remains to be established, but it does not correlate with measurable changes in the spectra of apolipoproteins associated with the emulsion remnants.

Animals↗

The effect of insulin deficiency on the metabolism of lipid emulsion models of triacylglycerol-rich lipoproteins in rats.

Groups of control rats and rats made insulin deficient by treatment with streptozotocin were injected intravenously (IV) with triacylglycerol-cholesteryl oleate-cholesterol-phospholipid emulsions designed to model the composition of triacylglycerol-rich lipoproteins. Insulin deficiency decreased the removal rates of emulsion triacylglycerol and cholesteryl ester whether fed a regular diet or a high-fat diet. Injection of heparin to stimulate the action of lipoprotein lipase increased the removal rates in both control and insulin-deficient rats, but control values were not restored by heparin given to insulin-deficient rats and compared with controls the difference due to insulin deficiency persisted. When emulsions were injected into functionally hepatectomized insulin-deficient rats the removal of the emulsion triacylglycerols was faster than in controls. Preformed remnants made in functionally hepatectomized donor rats were removed less rapidly after plasma injection into insulin-deficient rats than in control rats. If the remnants were isolated from the plasma by ultracentrifugation this effect disappeared. An emulsion with a supra-physiological content of unesterified cholesterol had increased efficiency of removal of emulsion core lipids from the plasma of insulin-deficient rats, but had negligible influence in control rats. These effects correlated with changes in the apolipoproteins associated with the lipid particles. Compared with control rat plasma, more of apolipoproteins AI and AIV and less of apolipoprotein E isoforms associated with emulsions exposed to insulin-deficient rat plasma.

Animals↗

Phosphatidylcholine metabolism after transfer from lipid emulsions injected intravenously in rats. Implications for high-density lipoprotein metabolism.

When injected intravenously in rats, emulsion models of triacylglycerol-rich lipoproteins were metabolized like natural lipoproteins and during the hydrolysis of emulsion triacylglycerols, a large fraction of the emulsion phosphatidylcholine was transferred to the plasma high-density lipoproteins. The removal from plasma of emulsion phosphatidylcholine was followed for 2 h in unanaesthetized rats. The half-lives for removal of phospholipid after injection of emulsions stabilized with dioleoylphosphatidylcholine or 1-palmitoyl-2-oleolyphosphatidylcholine were 58-63 min when traced with isologous label. In comparison, the published half-lives of HDL mixed phospholipids in rats are approx. 40 min, indicating that much of the clearance of the emulsion phospholipid could be accounted for by HDL catabolism. Measured LCAT activity was sufficient to account for not more than 2% of the catabolism of the HDL phospholipids labelled by this physiological procedure. Removal from plasma of label was more rapid when the same emulsions were labelled with tracer amounts of the heterologous dipalmitoylphosphatidylcholine, showing that individual phosphatidylcholine species were handled distinctly even when present only in tracer amounts in a bulk of another phosphatidylcholine differing in acyl chains.

Animals↗

The effect of added monoacylglycerols on the removal from plasma of chylomicron-like emulsions injected intravenously in rats.

Lipid emulsions were prepared with compositions similar to the triacylglycerol-rich plasma lipoproteins, but also incorporating added small amounts of monoacylglycerols. Control emulsions without monoacylglycerol were metabolized similarly to natural chylomicrons or very-low-density lipoproteins when injected intravenously in rats. The emulsion triacylglycerols and cholesteryl esters were both removed rapidly from the bloodstream, with the removal rates of triacylglycerols faster than those of cholesteryl esters. Much of the removed cholesteryl ester was found in the liver, but only a small fraction of the triacylglycerol, consistent with hepatic uptake of the triacylglycerol-depleted remnants of the injected emulsion. Emulsions incorporating added monooleoylglycerol or stearic acid were metabolized similarly. Added 1- or 2-monostearoylglycerol had no effect on triacylglycerol removal from plasma, but the removal rate of cholesteryl esters was decreased and less cholesteryl ester was found in the liver. These effects are similar to those recently described when emulsions and chylomicrons contained triacylglycerols with a saturated acyl chain at the glycerol 2-position, suggesting that saturated monoacylglycerol produced by the action of lipoprotein lipase may cause triacylglycerol-depleted remnant particles to remain in the plasma instead of being rapidly taken up by the liver.

Animals↗

Effects of phospholipid composition on the metabolism of triacylglycerol, cholesteryl ester and phosphatidylcholine from lipid emulsions injected intravenously in rats.

Lipid emulsions were prepared with a similar size and lipid composition to natural lymph chylomicrons, but in which the surface phospholipid was either egg phosphatidylcholine, dioleoyl-, dimyristoyl-, dipalmitoyl- or 1-palmitoyl-2-oleoylphosphatidylcholine (EYPC, DOPC, DMPC, DPPC or POPC). When injected into the bloodstream of conscious rats, the emulsions containing EYPC or POPC were metabolized similarly to natural chylomicrons, consistent with rapid lipoprotein lipase-mediated hydrolysis of triacylglycerols, followed by hepatic uptake of the remnants derived from the emulsions. Phospholipids from the injected emulsions were removed more slowly and became associated with the high-density lipoprotein fractions of the plasma. Emulsions containing DPPC were metabolized differently. Triacylglycerols disappeared very slowly from plasma, indicating lack of hydrolysis by lipoprotein lipase, and phospholipid radioactivity did not transfer to high-density lipoprotein. With emulsions containing DMPC, the plasma removal rates for emulsion triacylglycerols and cholesteryl esters were fast, but phospholipid radioactivity failed to transfer to the high-density lipoprotein fractions of plasma. With DOPC emulsions, clearances were slower than EYPC or POPC emulsions, but transfer to high-density lipoproteins was efficient. Therefore, an unsaturated chain at the glycerol 2-position was necessary for rapid hydrolysis by lipoprotein lipase and for efficient transfer of phospholipids to high-density lipoproteins. With an unsaturated chain at the glycerol 2-position, a saturated chain at the glycerol 1-position optimized the rate of remnant removal from the plasma.

Animals↗

The effect of triacyl-sn-glycerol structure on the metabolism of chylomicrons and triacylglycerol-rich emulsions in the rat.

A systematic study was undertaken to observe the effects of dietary (dioleoyl) triacyl-sn-glycerol structure on chylomicron composition and metabolism. First studied was a series of 1,2-dioleoyl-3-(saturated)acyl-sn-glycerols, where the fatty acid esterified at the 3-position was varied from 14 to 24 carbons. Next a series of 1,3-dioleoyl-2-acyl glycerols was studied, with various fatty acids esterified at the glycerol 2-position. These stereospecific triacyl-sn-glycerols were fed to donor rats and lymph chylomicrons were isolated, analyzed, and reinjected into recipient rats to study their disappearance from plasma and delivery to tissues. As shown by their compositions, chylomicrons obtained after feeding triacylglycerols containing all sn-3 fatty acid of chain length greater than 20 carbons were under-represented, possibly due to poorer digestion by lipases, or poorer absorption by the intestine. The 18-carbon saturated chain fatty acid (stearic acid) was equally well represented in chylomicrons whether in the 2- or 3-position of the fed triacylglycerol. The presence of increased amounts of long-chain saturated fatty acids in donor chylomicron triacylglycerols affected the metabolism of chylomicrons injected into the bloodstream of recipient rats. In particular the rate of removal of labeled cholesteryl esters, tracing removal of the partially degraded chylomicron remnants was slowed by the saturated chains, with palmitic acid and the 20-carbon fatty acid, arachidic acid, showing the most severe effects. There were clear differences in the removal from plasma of injected lymph chylomicrons derived from fed triacylglycerols containing stearic acid in either the 2- or 3-position, with evidence for remnants from the symmetrical triacylglycerols being less rapidly removed from the circulating blood. This effect was investigated further by injected model emulsions of chylomicrons, where the 2-position was substituted with saturated or transunsaturated acyl chains. Quantitation of removal from the blood stream of these model lipoproteins confirmed that a saturated or transunsaturated long chain fatty acid at the 2-position of the emulsion triacylglycerols slowed remnant removal from the blood. In some cases, with both lymph chylomicron and with emulsions, the lipolytic step mediated by lipoprotein lipase was also slowed.

Animals↗

Competition between chylomicrons and their remnants for plasma removal: a study with artificial emulsion models of chylomicrons.

In previous studies, protein-free emulsions of defined lipid composition were shown capable of simulating either the metabolism of chylomicrons (chylomicron-like emulsion) or their remnants (remnant-like emulsion), depending on the content of free, unesterified cholesterol. To validate further the assumption that remnant-like and chylomicron-like emulsion have metabolic pathways in common with their natural counterparts, studies of competition for plasma removal were undertaken: the remnant-like emulsion labeled with [3H]triolein was injected sequentially twice in the carotid arteries of rats to compare the clearance of remnant-like emulsion of the second injection with the first (control). Prior to the second injection, a large bolus of the chylomicron-like emulsion or rat lymph chylomicron was injected, to check the hypothesis that remnant generated from chylomicron-like emulsion or natural chylomicrons could compete with and displace remnant-like emulsion particles from their tissue receptor sites. Experiments were also performed in rats treated with Triton WR-1339, to block the generation of remnants. Results showed that remnants derived from either natural chylomicrons or chylomicron-like emulsion both strongly competed with the remnant-like emulsion. In contrast, when transformation of remnants was prevented by Triton, the undegraded particles of chylomicron-like emulsion or natural chylomicron were unable to compete with or displace remnant-like emulsion from its sites of removal from the plasma. In agreement with plasma clearance data, the hepatic uptake of the remnant-like emulsion was inhibited by the surplus dose of natural chylomicrons. In contrast, the spleen uptake was unaffected by it.

Animals↗

Uptake of artificial model remnant lipoprotein emulsions by the perfused rat liver.

In comparison with their precursor lipoproteins, the remanants of the triacylglycerol-rich lipoproteins are reduced in contents of triacylglycerols and apolipoproteins AI and AIV, whereas the contents of cholesterol (free and esterified) and apolipoprotien E are increased. In this study, lipid emulsion models of remnant lipoproteins were used to explore which of these factors are necessary for physiological rates of remnant uptake by the perfused rat liver. Uptake rates of lipid emulsion models of remnant lipoproteins in the presence of apolipoprotein E were similar to in vivo uptake rates.

Animals↗

Regulation of the metabolism of lipid emulsion model lipoproteins by a saturated acyl chain at the 2-position of triacylglycerol.

Lipid emulsion particles were prepared by sonicating four different lipid mixtures (triacylglycerol (TAG), 70%; phospholipid, 25%; cholesteryl oleate (CO), 3%; and free cholesterol, 2%), then purified by density gradient ultracentrifugation. For three test mixtures, the TAG contained 50, 75, or 100% 1,3-dioleyl-2-stearylglycerol (OSO) with the remainder being triolein (OOO); 100% triolein in the lipid mixture was used as the control. After intravenous injection of the lipid particles into unanesthetized rats, removal of radioactive TAG fatty acid and CO from plasma was measured for 30 min, then liver and spleen uptakes were measured. When emulsions contained 75% or 100% OSO as TAG, the plasma removal rates of CO were, respectively, 60% or 30% of the rate when the TAG was 100% triolein; smaller recoveries of CO were found in the liver. The clearances of TAG fatty acid did not differ significantly and the recoveries of TAG fatty acid in the organs were not affected by the type of emulsion injected. Remnant particles were derived from donor rats in which uptake was blocked by exclusion of liver and other viscera from the circulation before injection of 100% OOO and 100% OSO emulsions. When injected into recipient intact rats, the removal of remnants from plasma was slower for remnants derived 15 min after injection of 100% OSO emulsions than from 100% OOO emulsions, showing that the slower removal of emulsion CO was due to slower remnant uptake from the plasma with OSO emulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗

Cholesterol is necessary for triacylglycerol-phospholipid emulsions to mimic the metabolism of lipoproteins.

Emulsions with lipid compositions similar to the triacylglycerol-rich lipoproteins were metabolized similarly to natural chylomicrons or very-low-density lipoproteins when injected intravenously in rats. Radioactive labels tracing the emulsion triacylglycerols and cholesteryl esters were both removed rapidly from the blood stream, but the removal rate of triacylglycerols was faster than that of cholesteryl ester. Most of the removed cholesteryl ester label was found in the liver, but only a small fraction of the triacylglycerol label was found in this organ, consistent with hepatic uptake of the remnants of the injected emulsion. Emulsions otherwise identical but excluding unesterified cholesterol were metabolized differently. The plasma removal of triacylglycerols remained fast, but the cholesteryl esters were removed very slowly. Heparin stimulated lipolysis, but failed to increase the rate of removal of cholesteryl esters from emulsions lacking cholesterol. Evidently, emulsions lacking cholesterol were acted on by the enzyme lipoprotein lipase, but the resultant triacylglycerol-depleted remnant particle remained in the plasma instead of being rapidly taken up by the liver. Therefore, the presence of emulsion cholesterol is a critical determinant of early metabolic events, and the findings point to a similar role for cholesterol in the natural triacylglycerol-rich lipoproteins.

Animals↗

The effects of Triton WR-1339, protamine sulfate and heparin on the plasma removal of emulsion models of chylomicrons and remnants in rats.

Protein-free lipid emulsions with compositions modelling chylomicrons (chylomicron-like emulsion) or chylomicron remnants (remnant-like emulsion) were injected intra-arterially into nonanesthetized rats. Compared with control untreated rats, treatment with Triton WR-1339, protamine sulfate or heparin strongly modified the plasma removal of triacylglycerols and cholesteryl ester moieties of chylomicron-like emulsions, but had little effect on removal rates of triacylglycerols or cholesteryl esters of remnant-like emulsions. The effects on chylomicron-like removal were similar to those on natural lymph chylomicrons. The relative lack of effects on remnant-like emulsion removal provides additional evidence that remnant-like emulsions are a metabolic model for natural chylomicron remnants.

Animals↗

Structure and polymorphism of 18-carbon fatty acyl triacylglycerols: effect of unsaturation and substitution in the 2-position.

The polymorphic behavior of symmetric diacid triacylglycerols (TGs), 1,3-dioleoyl-2-stearoyl (OSO), 2-elaidoyl (OEO), and 2-vaccinoyl (OVO) glycerols were studied by differential scanning colorimetry (DSC) and X-ray diffraction and compared with the corresponding monoacid TGs triolein (OOO), tristearin (SSS), trielaidin (EEE), and trivaccinin (VVV). The monoacid TGs formed a bilayered structure in all the polymorphic forms. On quenching from the melt, the diacid TGs OEO and OVO formed a bilayered (D = 45 A) beta'-phase with the exception of OSO, which formed a hexagonally packed bilayered (D = 52 A) alpha-phase. At -7 degrees C, the alpha-phase of OSO quickly transformed to a bilayered (D = 45 A) beta'-phase. Incubation at the beta'-phase melting temperature transformed OVO, OEO, and OSO into a trilayered (D = 65 A) beta-phase, where the 1,3-dioleoyl chains are segregated from the vaccinoyl, elaidoyl, or stearoyl chains into alternating layers. In summary, when all the acyl chains in a TG are the same (saturated, cis or trans unsaturated), the stable beta-phase packs into a bilayered structure. However, when the 1- and 3-acyl chains are cis unsaturated (bent) and the 2-acyl chain is either saturated or trans-unsaturated (straight), a bilayered beta'-phase can form, but transforms to a stable trilayered beta-phase, where the 2-acyl chains form a layer between two different layers of 1,3-oleoyl chains.

Calorimetry, Differential Scanning↗

A kinetic model of chylomicron core lipid metabolism in rats: the effect of a single meal.

A detailed quantitative description of the metabolism of the core lipids of chylomicrons was developed with data obtained from rats injected intravenously with radioactive chylomicrons. Groups of recipient rats were starved or else fed a single meal that was either fat-free or contained 5% fat. The kinetic model included chains of delipidation compartments and a remnant particle. Compartments for recirculation of portions of triglyceride, cholesteryl ester, and unesterified fatty acid radioactivities were all included and necessary to obtain good fits to the data. Making the simplifying assumption that remnants could be represented as particles retaining cholesteryl esters but depleted in triglycerides, a 'delipidation index' was calculated as the ratio of the cholesteryl ester residence time divided by the triglyceride residence time. Significant differences were found in the delipidation index between the starved group and both the normal-fed and fat-free-fed groups. Compared with rats fed a meal of the usual diet which contained 5% fat, starved rats showed more extensive delipidation and a trend toward a longer residence time of remnant particles. A longer residence time of triglycerides in rats fed a fat-free meal was explained by less delipidation, but remnant removal appeared to be accelerated. The kinetic model makes possible an interpretation of the patterns of metabolism in terms of the known underlying physiological mechanisms.

Animals↗

Effects of cholesterol content on the metabolism of protein-free emulsion models of lipoproteins.

After intravenous injection, emulsions with compositions similar to chylomicrons behaved metabolically as described for chylomicrons, with faster removals of triacylglycerols than cholesteryl esters from the blood after injection into rats, and with greater uptakes of cholesteryl esters than triacylglycerols by the liver. In contrast, emulsions with a high content of free cholesterol showed equal removal rates from the blood of triacylglycerols and cholesteryl esters; and similar uptakes by the liver. This pattern of metabolism was that expected for a chylomicron core remnant particle. Emulsions poor in cholesteryl ester but rich in free cholesterol showed remnant-like behavior, whereas emulsions rich in cholesteryl ester but poor in free cholesterol were metabolized like nascent chylomicron particles. The amount of free cholesterol appeared to regulate metabolism by affecting the binding of apolipoproteins to the particle surface. Emulsions with a high content of free cholesterol bound less A-I, A-IV and C apolipoproteins, and the relative amount of apolipoprotein E was increased. All of these effects are consistent with the metabolic differences between chylomicrons and remnant particles, suggesting that the amount of free cholesterol plays a regulatory role in chylomicron metabolism.

Animals↗

Structure and polymorphism of 1,2-dioleoyl-3-acyl-sn-glycerols. Three- and six-layered structures.

Triacylglycerols, which usually contain at least one unsaturated fatty acid, are the most important forms of stored biological lipids in teleosts, mammals, and most plants. Since the physical properties of such mixed-chain triacylglycerols are poorly understood, a systematic study of such compounds has been initiated. Stereospecific 1,2-dioleoyl-3-acyl-sn-glycerols were synthesized with even carbon saturated fatty acyl chains of 14-24 carbons in length. Their polymorphic behavior was examined by differential scanning calorimetry and X-ray powder diffraction. The thermal behavior revealed from one to four major polymorphic transitions depending upon saturated chain length. Plots of enthalpy of fusion and entropy vs. carbon number for melting of the most stable polymorph were linear throughout the series with slopes of 1.0 kcal/mol per carbon atom and 2.6 cal/(mol K) per carbon atom, respectively. These slopes indicate that the saturated chains are packed in a well-ordered tightly packed lattice. When the compounds were rapidly cooled to 5 degrees C, X-ray powder diffraction revealed strong beta' (ca. 3.8 and 4.2 A) reflections and weak beta (ca. 4.6 A) reflections. The beta subcell reflections intensified when the compounds were heated to within 5 degrees C of the melting temperature of the highest melting polymorph. Evidence of an alpha phase was not seen on 30-min X-ray exposures for any of the compounds. In the proposed packing arrangement the saturated and unsaturated chains are segregated into layers. The stable form of all compounds exhibits a triple layer packing mode in which a bilayer of oleoyl chains is segregated from an interdigitated layer of saturated chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry↗

Metabolism of protein-free lipid emulsion models of chylomicrons in rats.

Emulsions were prepared by ultrasonication of mixtures of triolein, cholesteryl oleate, phosphatidylcholine and cholesterol in aqueous dispersions, then purified by ultracentrifugation. After injection into rats, the metabolism of the artificial, protein-free emulsions was comparable to the metabolism of chylomicrons collected from rat intestinal lymph during the absorption of fat. Like chylomicrons, the emulsion triacylglycerol was removed from the plasma more quickly than emulsion cholesteryl ester. Also like chylomicrons, much more emulsion cholesteryl ester than triacylglycerol appeared in the liver 10 min after injection, and only trace amounts appeared in the spleen. Because the artificial emulsions gained apolipoproteins when incubated with plasma, their metabolism was probably facilitated by the recipient rat plasma apolipoproteins and so, in rats made apolipoprotein-deficient by treatment with estrogen, the removal of emulsions from the plasma was slowed. Removal was also slowed in hyperlipidemic rats fed a high-fat, high-cholesterol diet to expand the plasma pools of the triacylglycerol-rich lipoproteins and remnants. The results indicate that the metabolism of lymph chylomicrons can be modeled by artificial, protein-free lipid emulsions not only in the initial partial hydrolysis by lipoprotein lipase, but also in the delivery of a remnant-like particle to the liver.

Animals↗

Synthesis and polymorphism of 3-acyl-sn-glycerols.

3-Acyl-sn-glycerols with even-numbered saturated fatty acyl chains from decanoate to lignocerate were synthesized. Successful hydrolysis of the long acyl chain intermediate 1,2-isopropylidene-3-acyl-sn-glycerols from stearate to lignocerate was accomplished by applying the compounds to silica gel and exposing them to hydrogen chloride gas at -75 degrees C. The purity of the compounds was checked by boric acid impregnated thin-layer chromatography, 13C NMR, and reverse-phase high-pressure liquid chromatography. Differential scanning calorimetry and X-ray diffraction techniques were used to study the polymorphism of the compounds. In the beta phase obtained from solvent of crystallization, the acyl chain packing was in a two-dimensional oblique lattice with specific chain-chain interactions with a tilt angle of 55.4 degrees from the bilayer plane. The thickness of the region containing two glycerol head groups was 12.7 A. The phase transition enthalpy of melting for the beta phase was 1.06 kcal/mol of CH2. On being cooled these compounds crystallized reversibly to an unstable alpha phase, which on being further cooled underwent a second crystallization to a beta or beta' phase. The thermodynamic parameters and long spacings of these compounds in both beta and alpha phases were linear, indicating isostructural packing in each phase. The enthalpy of the melting transition of the alpha phase was 0.69 kcal/mol of CH2. In this phase, the chains were packed in a hexagonal lattice with nonspecific chain-chain interactions. The thickness of the head-group region (12.2 A) and the tilt angle (55 degrees) of the acyl chains in the alpha phase were very similar to those in the beta phase.

Calorimetry↗

Tumor-associated metabolism in the rat is a unique physiologic entity.

The metabolic responses associated with the tumor-bearing state, as compared to states of sepsis and prolonged starvation, were examined. Tumor-bearing rats manifested significant elevation of triglycerides, significant reduction of glucose and insulin levels, significantly increased plasma skeletal muscle proteolysis-inducing activity, and an unchanged hepatic protein synthetic activity compared to control rats. Prolonged starvation produced an adaptation characterized by significant hypoglycemia and hypoinsulinemia, reduced hepatic protein synthesis, and increased peripheral protolysis compared to controls. Septic animals had glucose, insulin, and lipid levels similar to control animals but had increased hepatic protein synthesis. Each state manifested its own unique metabolic response compared to controls. It appears that the metabolic consequences of cancer in this sarcoma rat model is different than septic and prolonged starvation states.

Animals↗