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International audience; Plant-based proteins are generally characterised by lower Indispensable Amino Acid (IAA) content, digestibility, and anabolic properties, compared to animal-based proteins. However, they are environmentally friendlier, and wider consumption is advocated. Older adults have higher dietary protein needs to prevent sarcopenia, a disease marked by an accelerated loss of muscle mass and function. Given the lower environmental footprint of plant-based proteins and the importance of optimising dietary protein quality among older adults, this paper aims to assess the net peripheral Amino Acid (AA) appearance after ingestion of three different plant protein and fibre (PPF) products, compared to whey protein with added fibre (WPF), in healthy older adults. In a randomised, single-blind, crossover design, nine healthy men and women aged ≥65 years consumed four test meals balanced in AA according to the FAO reference protein for humans, matched for leucine, to optimally stimulate muscle protein synthesis in older adults. A fasted blood sample was drawn at each visit before consuming the test meal, followed by postprandial arterialise blood sampling every 30 min for 3 h. The test meal was composed of a soup containing either WPF or PPF 1–3. The PPF blends comprised pea proteins with varying additional rice, pumpkin, soy, oat, and/or almond protein. PPF product ingestion resulted in a lower maximal increase of postprandial leucine concentration and the sum of branched-chain AA (BCAA) and IAA concentrations, compared to WPF, with no effect on their incremental area under the curve. Plasma methionine and cysteine, and to a lesser extent threonine, appearance were limited after consuming the PPF products, but not WPF. Despite equal leucine doses, the WPF induced greater postprandial insulin concentrations than the PPF products. In conclusion, the postprandial appearance of AA is highly dependent on the protein source in older adults, despite providing equivalent IAA levels and dietary fibre. Coupled with lower insulin concentrations, this could imply less anabolic potential. Further investigation is required to understand the applicability of plant-based proteins in healthy older adults.

International audience; Food matrix interactions with polyphenols can affect their bioavailability and as a consequence may modulate their biological effects. The aim of this study was to determine if the matrix and its processing would modulate the bioavailability and the postprandial nutrigenomic response to a dietary inflammatory stress of apple flavan-3-ol monomers. We carried out an acute randomized controlled study in minipigs challenged with a high fat meal (HFM) supplemented with raw fruit, puree, or apple phenolic extract with matched content of flavan-3-ol monomers. Fasting and postprandial blood samples were collected over 3 h to quantify flavan-3-ol monomers in sera by UPLC-Q-TOF/MS and to isolate peripheral blood mononuclear cells (PBMCs) for assessing the changes in the gene expression profile using a microarray analysis. When compared to the extract-supplemented meal, the peak of the total flavan-3-ol concentration was reduced by half with both raw apple and puree supplements. The apple matrices also affected the gene expression profile as revealed by the Principal Component Analysis of the microarray data from PBMCs which discriminated the supplementation of HFM with the polyphenol extract from those with raw apples or puree. A total of 309 genes were identified as differentially expressed by the apple-derived products compared to HFM, with 63% modulated only in the presence of the food matrix (apple and puree). The number of differentially modulated genes was higher with the puree (246) than with the unprocessed apple (182). Pathway enrichment analyses revealed that genes affected by the apple-derived products control inflammation and leukocyte transendothelial migration both involved in the onset of atherosclerotic processes. Overall, this study showed that the two apple matrices reduce the postprandial serum concentration of flavon-3-ols whereas they increase the nutrigenomic response of PBMCs. The biological processes identified as modulated by the apple products suggest an attenuation of the transient proinflammatory response induced by a HFM. The differences observed between the nutrigenomic responses support that the apple matrix and its processing affect the nutrigenomic response, probably by increasing the bioavailability of other apple phytochemicals. To conclude, this study raises awareness for considering the impact of the food matrix and its processing on the biological response of polyphenols in nutritional studies.

International audience; Purpose We examined the impact of matrix food structure on post-prandial folate bioavailability (and other macronutrients) in human volunteers using a randomized, controlled, crossover experimental design. Methods Twelve healthy male volunteers (22.6 ± 0.4 years old) were offered four food models (differing in matrix structure: Custard, Pudding, Sponge cake and Biscuit) to which 1 mg of folic acid was added, according to a randomized, controlled, crossover experimental design. Plasma folates, glucose, insulin, alpha amino nitrogen and triglycerides were measured over the post-prandial period (from T0 to T480 min). Results Food matrix structure was capable of altering folate plasma availability. The highest folate availability was observed for pudding and to a lesser extent Sponge cake whereas the lowest was for the two matrices presenting extreme rheological properties: Custard (liquid) (P < 0.05 total AUC) and to a lesser extent Biscuit (hard solid) (P < 0.05, AUC 180 min). The analysis of plasma kinetics of appearance of other nutrients/metabolites helps to understand/explain the lower bioavailability of folates in Custard and Biscuit. Conclusion A least overall efficient bio-accessibility of all macronutrients and folic acid is observed in the gut lumen for Biscuit (delayed/incomplete destructuration of biscuit along the digestive tract). On the contrary, the lower folic acid absorption observed with custard does not fit with the rapid plasma appearance of other nutrients and should require further investigation.

International audience; Scope: The specific effect of the food matrix structure on fat-soluble micronutrient bioavailability is only partly understood. Evaluating fat-soluble micronutrient bioavailability after consumption of foods displaying similar composition but different structure is aimed at. Methods and results: Twelve healthy subjects are enrolled in a randomized, open label, crossover postprandial trial. Four different model foods are tested: custard, pudding, sponge cake, and biscuit. Vitamin D 3 , lutein, and triglyceride chylomicron responses, evaluated as postprandial areas under the curve, are then assayed. Custard triglyceride response is higher than pudding and biscuit responses (up to +122.7%, p < 0.0001). Sponge cake vitamin D 3 response is higher than biscuit response (+26.6%, p = 0.047). No difference between the model foods are observed regarding lutein responses. Triglyceride responses peak at 3 h for all conditions, while vitamin D 3 and lutein peaks are delayed by 1 h with the biscuit matrix compared to other model foods. Conclusion: Food structure can significantly impact on triglyceride and vitamin D 3 bioavailability in terms of absorbed amounts and/or maximum absorption time. The data highlight positive correlations between triglyceride, vitamin D, and lutein nutrient responses. These results are of particular interest to develop functional foods for population subgroups such as the elderly.

This work was supported by an INRA Priority Action of the "Alimentation Humaine" department (2013-2015). Marielle Margier received a doctoral fellowship (2015-2018) from Region PACA in partnership with the Centre Technique de Conservation des Produits Alimentaires (CTCPA, Avignon); Scope: Food matrix is generally believed to alter carotenoid bioavailability, but its effect on xanthophylls is usually limited. This study thus aims to decipher the digestion-absorption process of lutein in the presence or not of a food matrix.Methods: Lutein transfer to gastric-like lipid droplets or artificial mixed micelles was assessed when lutein was added to test meals either as a pure molecule ((all-E)-lutein) or in canned spinach ((Z) + (all-E)-lutein). The obtained mixed micelles were delivered to Caco-2 cells to evaluate lutein uptake. Finally postprandial plasma lutein responses were compared in minipigs after the two test meals.Results: Lutein transfer to gastric-like lipid droplets and to mixed micelles was higher when lutein was added in spinach than when it was added as pure lutein (+614% and +147%, respectively, p < 0.05). Conversely, lutein uptake was less effective when micellar lutein was from a meal containing spinach than from a meal containing its pure form (-55%, p < 0.05). In minipigs, postprandial lutein response was delayed with spinach but not significantly different after the two test meals.Conclusion: Opposite effects at the micellarization and intestinal cell uptake steps explain the lack of effect of spinach matrix on lutein bioavailability.

Ageing impairs the muscle anabolic effect of food intake, which may explain muscle loss and an increased risk of sarcopenia. Ageing is also associated with low grade inflammation (LGI), which has been negatively correlated with muscle mass and strength. In rodents, the muscle anabolic resistance observed during ageing and sarcopenia has been ascribed to the development of the LGI. We aimed to investigate this relationship in humans. We studied protein metabolism and physical fitness in healthy elderly volunteers with slight chronic C-reactive protein. Two groups of healthy elderly volunteers were selected on the presence (or not) of a chronic, slight, elevation of CRP (Control: 2 mg l(-1) and

International audience; Background: Meat cooking conditions in in vitro and in vivo models have been shown to influence the rate of protein digestion, which is known to affect postprandial protein metabolism in the elderly.Objective: The present study was conducted to demonstrate the effect of cooking conditions on meat protein assimilation in the elderly. We used a single-meal protocol to assess the meat protein absorption rate and estimate postprandial meat protein utilization in elderly subjects.Design: The study recruited 10 elderly volunteers aged 70–82 y. Each received, on 2 separate occasions, a test meal exclusively composed of intrinsically 15N-labeled bovine meat (30 g protein), cooked at 55°C for 5 min [rare meat (RM)] or at 90°C for 30 min [fully cooked meat (FCM)], and minced. Whole-body fluxes of leucine, before and after the meal, were determined with the use of a [1-13C]leucine intravenous infusion. Meat protein absorption was recorded with the use of 15N enrichment of amino acids.Results: Postprandial time course observations showed a lower concentration in the plasma of indispensable amino acids (P < 0.01), a lower entry rate of meat leucine in the plasma (P < 0.01), and a lower contribution of meat nitrogen to plasma amino acid nitrogen (P < 0.001), evidencing lower peripheral bioavailability of meat amino acids with RM than with FCM. This was associated with decreased postprandial whole-body protein synthesis with RM than with FCM (40% compared with 56% of leucine intake, respectively; P < 0.01).Conclusions: Whereas meat cooking conditions have little effect on postprandial protein utilization in young adults, the present work showed that the bioavailability and assimilation of meat amino acids in the elderly is lower when meat is poorly cooked. In view to preventing sarcopenia, elderly subjects should be advised to favor the consumption of well-cooked meat. This trial was registered at clinicaltrials.gov as NCT02157805.

The authors are very grateful to the physician and nurses of the Human Nutrition Research Centre of Auvergne and to Patrice Reiling for their technical assistance; International audience; Lycopene (LYC) bioavailability is relatively low and highly variable, because of the influence of several factors. Recent in vitro data have suggested that dietary Ca can impair LYC micellarisation, but there is no evidence whether this can lead to decreased LYC absorption efficiency in humans. Our objective was to assess whether a nutritional dose of Ca impairs dietary LYC bioavailability and to study the mechanism(s) involved. First, in a randomised, two-way cross-over study, ten healthy adults consumed either a test meal that provided 19-mg (all-E)-LYC from tomato paste or the same meal plus 500-mg calcium carbonate as a supplement. Plasma LYC concentration was measured at regular time intervals over 7 h postprandially. In a second approach, an in vitro digestion model was used to assess the effect of increasing Ca doses on LYC micellarisation and on the size and zeta potential of the mixed micelles produced during digestion of a complex food matrix. LYC bioavailability was diminished by 83 % following the addition of Ca in the test meal. In vitro, Ca affected neither LYC micellarisation nor mixed micelle size but it decreased the absolute value of their charge by 39 %. In conclusion, a nutritional dose of Ca can impair dietary LYC bioavailability in healthy humans. This inhibition could be due to the fact that Ca diminishes the electrical charge of micelles. These results call for a thorough assessment of the effects of Ca, or other divalent minerals, on the bioavailability of other carotenoids and lipophilic micronutrients.

The free radical theory of aging proposes that oxidative stress plays a key role in the aging process. By altering muscle protein degradation rates, it could accelerate the age-related loss of muscle proteins. Glutathione (GSH), one of the main body antioxidants, could prevent this phenomenon, but its concentration decreases during aging. Our aims were to have a better understanding of the mechanisms of the age-related decrease in glutathione availability and of the links with sarcopenia. Male Wistar rats aged 6, 9, 12, 15, 19, 22, 25 and 28 months (n = 6 per age) were used to measure plasma and skeletal muscle protein carbonyl content, plasma total and free cyst(e)ine content, liver and muscle glutathione content as well as liver GSSG reductase, GSH peroxidase, GSH transferase and gamma glutamyl cysteine synthetase (GCS) activities. Although tissue glutathione content decreased with age, the other markers of oxidative stress were little changed during aging. In particular, muscle protein carbonyl content was unchanged. Variations in glutathione availability were not explained by cyst(e)ine availability but depended on gamma GCS activity. The stability of skeletal muscle carbonyl content during aging suggests a very efficient degradation of oxidized proteins in muscle.

Inflammatory bowel diseases (IBDs) are associated with an increased whole-body protein turnover. In certain drug-induced experimental models of IBD, disturbances of protein synthesis in tissues have been reported recently, but it is unclear if similar disturbances occur in other chronic intestinal diseases. Therefore we investigated changes in protein synthesis in different tissues of HLA-B27 (human leucocyte antigen B27) transgenic rats that develop spontaneously chronic inflammation, with major involvement of the colon. Protein synthesis rate in HLA-B27 rats was shown to be higher in nine different tissues compared with control (Fisher 344) rats. The absolute rate of protein synthesis was highly stimulated at the main inflammatory site (+290% in the colon). However, liver, muscle and skin appeared to be major contributors to the increased protein synthesis observed at the whole-body level. Despite the increased protein synthesis, HLA-B27 rats presented a marked atrophy of muscles, which suggests an increased proteolysis. These results contrast with metabolic disturbances described in acute inflammation and colitis induced by drugs (i.e. dextran sodium sulphate). The present study suggests that the modifications of protein metabolism are strongly influenced by the type of the inflammatory diseases and thus by the underlying mechanisms, which result in different metabolic adaptations and specific nutritional requirements.

Publication Inra prise en compte dans l'analyse bibliométrique des publications scientifiques mondiales sur les Fruits, les Légumes et la Pomme de terre. Période 2000-2012. http://prodinra.inra.fr/record/256699; International audience; The aim of the present study was to determine whether the addition of soluble fibre in the diet affected protein metabolism in the intestinal tissues, some visceral organs and in skeletal muscle. A diet supplemented with pectin (80 g/kg) was fed to young growing rats and the effect on organ mass and protein metabolism in liver, spleen, small and large intestines and gastrocnemius muscle was monitored and compared with the control group. Protein synthesis rates were determined by measuring [13C]valine incorporation in tissue protein. In the pectin-fed rats compared with the controls, DM intake and body weight gain were reduced (9 and 20 %, respectively) as well as gastrocnemius muscle, liver and spleen weights (6, 14 and 11 %, respectively), but the intestinal tissues were increased (64 %). In the intestinal tissues all protein metabolism parameters (protein and RNA content, protein synthesis rate and translational efficiency) were increased in the pectin group. In liver the translational efficiency was also increased, whereas its protein and RNA contents were reduced in the pectin group. In gastrocnemius muscle, protein content, fractional and absolute protein synthesis rates and translational efficiency were lower in the pectin group. The stimulation of protein turnover in intestines and liver by soluble fibre such as pectins could be one of the factors that explain the decrease in muscle turnover and whole-body growth rate.

International audience; BACKGROUND: The rate of protein digestion affects protein utilization in elderly subjects. Although meat is a widely consumed protein source, little is known of its digestion rate and how it can be affected by the chewing capacity of elderly subjects. OBJECTIVES: We used a [1-(13)C]leucine balance with a single-meal protocol to assess the absorption rate of meat protein and to estimate the utilization of meat protein in elderly subjects with different chewing efficiency. DESIGN: Twenty elderly volunteers aged 60-75 y were involved in the study. Ten of them had healthy natural dentition, and the other 10 were edentulous and wore complete dentures. Whole-body fluxes of leucine, before and after the meal (120 g beef meat), were measured with the use of a [1-(13)C]leucine intravenous infusion. RESULTS: A rapid increase in plasma aminoacidemia and plasma leucine entry rate was observed after meat intake in dentate subjects. In complete denture wearers the increase in leucine entry rate was delayed (P

International audience; BACKGROUND: Inflammation is known to affect sulfur amino acid metabolism. Aging is associated with an increased prevalence of inflammatory conditions, but the metabolism of methionine has been poorly explored in the elderly. OBJECTIVES: The aims of this study were to compare methionine kinetics between elderly and young subjects and to explore the effect of aging on the response to a mild inflammatory challenge induced by a vaccination. DESIGN: Seven elderly volunteers aged 66-76 y and 8 young volunteers aged 22-26 y were studied before and 2 d after a vaccination (diphtheria, tetanus, poliomyelitis, and typhoid vaccines). Methionine kinetics were measured by using an infusion of L-[1-13C, methyl-2H3]methionine in the postabsorptive and fed states. RESULTS: Before vaccination, the contribution of homocysteine remethylation to methionine-methyl flux (Qm) and the ratio of remethylation to homocysteine transsulfuration were significantly lower in the elderly subjects than in the young subjects (P < 0.05). In contrast, the contribution of transsulfuration to methionine transmethylation was higher in the elderly (P < 0.05). Vaccination significantly increased the ratio of transsulfuration to transmethylation and decreased the ratio of remethylation to Qm (P < 0.05). CONCLUSIONS: The preferential methionine metabolism toward cysteine synthesis observed after vaccination suggests an increased requirement of sulfur amino acids even in mild inflammatory situations. The main finding of this study is a higher proportion of methionine entering the transsulfuration pathway in elderly subjects before vaccination. This finding suggests an increased cysteine demand during aging.

Article original; International audience; BACKGROUND AND AIMS: Muscle wasting and increased synthesis of proteins and compounds involved in host defense characterize severe injury. The aims of the studies reported were to determine which amino acids exhibited an increased tissue content linked to anabolic processes in infected rats by comparison with healthy pair-fed controls, and to explore whether diets supplemented with these amino acids attenuate the catabolic response to infection. METHODS: Total amino acid content of the liver and the rest of the body were measured in control well-fed rats, in infected rats and their pair-fed controls 2 days after infection. In the nutritional protocols, infected rats were fed with a diet supplemented with alanine (basal diet), or threonine, serine, aspartate, asparagine and arginine (AA) or AA+cysteine (complete diet). RESULTS: Infection significantly increased liver total amino acid content by 38% for most amino acids. In contrast, the percentage increase was cysteine 79.3, threonine 45.3, aspartate-asparagine 46.3 and serine 46.5. Whole body without liver content of most amino acids decreased after infection due to the catabolic response, while the content of cysteine increased by 6% (P

Mitochondrial free radical (ROS) production could be involved in sarcopenia. Our aim was to measure this production in various muscles during aging. Male Wistar rats aged 4.5 and 24 months were used. H(2)O(2) release and protein carbonyls were evaluated in isolated mitochondria from an oxidative (soleus) and a glycolytic (tibialis anterior) muscle. Total and Mn-superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX) and glutathione reductase (GR) activities were measured in tibialis anterior. In soleus, glutamate/malate supported mitochondrial H(2)O(2) release was lower than in tibialis anterior in young rats, but increased significantly with age. In tibialis anterior, glutamate/malate or succinate supported H(2)O(2) release was unchanged with age. ROS generators were complexes I and III. Mitochondrial carbonyl content remained stable during aging in both muscles but tended to be higher in tibialis anterior than in soleus. Tibialis anterior total SOD (+17%), catalase (+84%), and GPX (-17%) activities varied significantly with age but Mn-SOD was unchanged, suggesting an increase in cytosolic ROS production. In conclusion, the higher life-long H(2)O(2) release observed in tibialis anterior is consistent with the known sensitivity of glycolytic muscles to sarcopenia. The fact that the rate of H(2)O(2) release increases with age in soleus seems to have little impact.

The mechanisms leading to hypoalbuminemia in sepsis were explored by measuring plasma volume, albumin distribution, plasma albumin transcapillary escape rate (TER), and efflux (TER × albumin intravascular pool). These parameters were quantified in infected rats, injected intravenously with live Escherichia coli, and pair-fed and well-fed rats using an injection of35S-albumin and measuring plasma and whole body albumin concentrations. Animals were studied on days 1, 6, and 10 after infection. In pair-fed rats, neither albumin distribution nor exchange rate between the intra- and extravascular compartments was modified. The increase of plasma volume after infection partly explained hypoalbuminemia. Infection resulted in a reduction of the total albumin pool of the body all along the experimental period, indicating a net loss of the protein. Albumin TER (%/day) was significantly increased 1 and 6 days after infection, but the absolute efflux was increased only on day 1. Normal values were observed on day 10. Therefore, an accelerated plasma efflux contributes to hypoalbuminemia only during the early period of sepsis. During this phase, the protein was retained in the extravascular space where it was probably catabolized. Later on, other factors are probably involved.

International audience; BACKGROUND & AIM: Polytrauma patients are characterized by a negative nitrogen balance and muscle wasting. Standard nutrition is relatively inefficient to improve muscle protein turnover. The aim of this study was to investigate the effect of enteral nutrition (EN) supplemented with specific amino acids on protein metabolism in polytrauma patients. METHODS: In a double blind study, 12 polytrauma patients were randomized to receive EN supplemented with either a mixture of cysteine, threonine, serine and aspartate (AA patients) or alanine at isonitrogenous levels (Ala patients). An intravenous infusion of l-[1-(13)C]-leucine was performed in the fed state between day 9 and 12 post-injury (Df) in patients and in a group of healthy volunteers (n=8) (EN+Ala) to measure whole body leucine kinetics, plasma and muscle protein synthesis rates. Nitrogen balance, 3-methyl histidine excretion were measured from day 3 to Df. RESULTS: The contribution of total plasma proteins to whole body protein synthesis was greatly increased, from 11% in healthy volunteers to about 25% in polytrauma patients. AA supplementation had no effect on nitrogen balance, leucine kinetics or plasma protein synthesis in patients. In contrast, the urinary excretion of 3-methyl histidine tended to decrease along the study in the AA supplemented group compared to an increase in the Ala group. Muscle protein synthesis tended to be higher in the AA group than in the Ala group (46%, P=0.065). CONCLUSION: During injury, an increased supply of cysteine, threonine, serine and aspartate could be able to better cover the specific amino requirements, thus resulting in improved muscle protein synthesis without impairment of acute phase protein synthesis.

Methionine transsulfuration in plasma and liver, and plasma methionine and cysteine kinetics were investigated in vivo during the acute phase of sepsis in rats. Rats were infected with an intravenous injection of live Escherichia coli, and control pair-fed rats were injected with saline. Two days after injection, the rats were infused for 6 h with [35S]methionine and [15N]cysteine. Transsulfuration was measured from the transfer rate of 35S from methionine to cysteine. Liver cystathionase activity was also measured. Infection significantly increased ( P < 0.05) the contribution of transsulfuration to cysteine flux in both plasma and liver (by 80%) and the contribution of transsulfuration to plasma methionine flux (by 133%). Transsulfuration measured in plasma was significantly ( P < 0.05) higher in infected rats than in pair-fed rats (0.68 and 0.25 μmol · h−1 · 100 g−1, respectively). However, liver cystathionase specific activity was decreased by 17% by infection ( P < 0.05). Infection increased methionine flux (16%, P < 0.05) less than cysteine flux (38%, P < 0.05). Therefore, the plasma cysteine flux was higher than that predicted from estimates of protein turnover based on methionine data, probably because of enhanced glutathione turnover. Taken together, these results suggest an increased cysteine requirement in infection.

We investigated the ability of pentoxifylline (PTX) to modulate protein synthesis and degradation in the presence and absence of insulin during incubation of epitrochlearis muscle, 2 or 6 days after injection of Escherichia coli. On days 2 and 6 after infection, protein synthesis was inhibited by 25%, whereas proteolysis was enhanced by 75%. Insulin (2 nM) in vitro stimulated protein synthesis in muscles from infected rats to the same extent as in controls. The ability of insulin to limit protein degradation was severely blunted 48 h after infection. On day 6 after infection, insulin inhibited proteolysis to a greater extent than on day 2. PTX suppressed the increase in plasma concentrations of tumor necrosis factor more than 600-fold after injection of bacteria, and partially prevented the inhibition of protein synthesis and stimulation of protein degradation during sepsis. Moreover, PTX administration maintained the responsiveness of protein degradation to insulin during sepsis. Thus cytokines may influence skeletal muscle protein metabolism during sepsis, both indirectly through inhibition of the effects of insulin on proteolysis, and directly on the protein synthesis and degradation machinery.

Skeletal muscle catabolism is a characteristic metabolic response to sepsis. We investigated the ability of physiological insulin (2 nM) or insulin-like growth factor I (IGF-I, 10 nM) concentrations to modify protein metabolism during incubation of epitrochlearis 2, 6, or 15 days after injection of live Escherichia coli. On days 2 and 6 postinfection, skeletal muscle exhibited an exacerbated negative protein balance resulting from both an inhibition in protein synthesis (25%) and an enhanced proteolysis (90%) compared with controls. By day 15 postinfection, protein balance in infected rats was significantly improved compared with either day 2 or 6. At this time, protein synthesis was augmented and protein degradation was decreased in infected rats relative to day 6. Insulin or IGF-I stimulated protein synthesis in muscles from septic and control rats in vitro to the same extent at each time point examined. The ability of insulin or IGF-I to limit protein degradation was severely blunted 48 h after infection. On day 6 postinfection, the effect of insulin or IGF-I to inhibit proteolysis was more pronounced than on day 2. Incubation with IGF-I limited proteolysis to a greater extent than insulin on both days in infected but not control rats. By day 15, insulin diminished proteolysis to the same extent as in controls. The results suggest that injection of bacteria causes fundamental derangements in protein metabolism that persist for days after infection.