Changes In Protein Metabolism Research Articles

Protein Metabolism in Acromegaly: Differential Effects of Short- and Long-Term Treatment

GH acutely increases body protein by stimulating protein synthesis and reducing protein oxidation. The objective of the study was to determine whether these changes in protein metabolism are sustained in long-term GH excess and reversed by correction. We conducted a cross-sectional study in 16 acromegalic and 18 normal subjects and a longitudinal study in which acromegalic subjects were studied before and after short-term (n=8) or long-term (n=10) treatment. The study was conducted at a clinical research center. Whole-body rates of leucine appearance (leucine Ra; an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (NOLD; an index of protein synthesis) estimated using infusion of 1-[13C] leucine were measured. Leucine Ra and NOLD were greater (P<0.01) in acromegalic compared with normal subjects, whereas leucine oxidation did not differ. Leucine oxidation increased significantly (P<0.05) after short-term treatment but returned to baseline after long-term treatment. Both leucine Ra and NOLD decreased significantly (P<0.05) after short- and long-term treatment. Adjustment for body composition did not affect results. In acromegalic subjects, protein breakdown and synthesis are increased, whereas protein oxidation does not differ from normal subjects. Protein oxidation increases transiently, whereas protein breakdown and synthesis are stably reduced after treatment. Because protein oxidation represents irreversible loss, we conclude that the normal state of protein oxidation found in acromegaly and after long-term treatment represents metabolic adaptation, which maintains protein mass at a steady state after stable changes in GH status.

Protein Metabolism and Endurance Exercise

Prolonged endurance exercise stimulates whole-body protein turnover (synthesis and degradation) but it remains contentious whether this translates into an increased net protein oxidation or dietary requirement for protein. Skeletal muscle is the major energy consumer during exercise and the oxidation of branched-chain amino acids (BCAA) is increased several-fold, suggesting an increased requirement for fuel. Increased BCAA oxidation has been proposed to impair aerobic energy provision during prolonged exercise, but there is little evidence to support this theory. Endurance training blunts the acute exercise-induced increase in whole-body protein turnover and skeletal BCAA oxidation at a given work intensity. However, training also increases the maximal capacity for skeletal muscle BCAA oxidation, as evidenced by a higher maximal activity of the rate-determining enzyme branched-chain oxo acid dehydrogenase. Exercise-induced changes in protein metabolism are affected by nutritional status, with high carbohydrate availability (as typically practiced by endurance athletes) generally associated with reduced net protein utilisation. Ingestion of protein with carbohydrate improves net protein balance during exercise and recovery compared with carbohydrate alone, but it remains to be determined whether this practice facilitates the adaptive response to chronic training.

Glutamine supplementation in the newborn infant

Glutamine is a non-essential amino acid that can be synthesized de novo from glutamate. This synthesis can be increased by intravenous infusion of carbon precursors (alpha-ketoglutarate or amino acids) in adults and in infants. The metabolism of glutamine is highly compartmentalized between the splanchnic tissues and the periphery, so that orally administered glutamine is completely metabolized in the splanchnic compartment. Data from studies in adults and children show that plasma levels of glutamine decline during acute stress and illness. Because of its importance in several physiological functions (the demonstrated benefits of supplemental glutamine in adult burns and trauma patients and the inhibitory effect on proteolysis in the skeletal muscle in vitro), it has been suggested that during 'acute stress' the demands of glutamine outweigh its de novo synthesis, resulting in a fall in plasma glutamine levels. As a consequence, glutamine has been considered a 'conditionally essential' amino acid. Because of its instability in solution, glutamine is not routinely added to the parenteral amino acid mixtures. A number of clinical trials of parenteral and enteral supplementation of glutamine have been performed. The outcome measures examined have varied between acute effects and long-term complex clinical events such as mortality and risk of infections. Although acute studies in LBW babies have shown some beneficial effects such as changes in protein metabolism and activation of immune system, these have not been translated into prolonged advantages such as reduction in mortality or in nosocomial infection. The reasons for these differences are discussed.

Metabolic Adjustments to Varying Protein Intake in Harbor Seals (Phoca vitulina): Evidence from Serum Free Amino Acids

Effects of varying dietary protein intake on serum free amino acid (FAA) concentrations were studied in harbor seals (Phoca vitulina) fed two different prey fish diets: either exclusively low-fat, high-protein walleye pollock (Theragra chalcogramma) or high-fat, relatively high-energy-density Pacific herring (Clupea pallasi). Significant differences in FAA concentrations and patterns were observed between the two diets. All essential amino acids (EAA), except methionine and phenylalanine, and two nonessential amino acids (NEAA), glycine and tyrosine, decreased when the diet was switched from herring to pollock and increased on switching back to herring. Both total EAA concentrations and EAA : NEAA ratios decreased with the elevated protein intake typical of a low-fat pollock diet, indicating an inverse correlation between EAA concentrations and dietary protein intake levels. We propose that differing dietary protein intake, caused by differences in macronutrient composition of the two prey fish species, induced a change in protein metabolism that was reflected in blood-circulating amino acids. These findings suggest that surveys of amino acid profiles may be useful to partially determine the protein metabolic status of harbor seals.

Bed rest and myopathies

The loss of skeletal muscle with injury or critical illness can be dramatic. This review emphasizes the importance of skeletal muscle as a metabolic reserve. Changes in protein metabolism with bed rest alone and during physiological stress are discussed. Nutritional and hormonal interventions that ameliorate the loss of skeletal muscle are highlighted. The loss of skeletal muscle that occurs with inactivity alone can be prevented by nutritional supplementation with an essential amino acid formula. Bed rest with accompanying hypercortisolemia produces a threefold greater loss of skeletal muscle than bed rest alone. Essential amino acids stimulate muscle anabolism during acute hypercortisolemia; however, their effects during chronic hypercortisolemia must be explored. Skeletal muscle loss with trauma or critical illness is due in great part to the interaction of bed rest (muscular inactivity) and stress (hypercortisolemia). Younger individuals respond to nutritional and pharmacological interventions during bed rest alone. Given a lower relative lean mass in the elderly and the importance of skeletal muscle as a metabolic reserve during stress, it is understandable that clinical outcomes are worse in older patients. Countermeasures to the loss of skeletal muscle, especially in the stressed patient, must be developed.

Proteolytic Mechanisms, Not Malnutrition, Cause Loss of Muscle Mass in Kidney Failure

Hypoalbuminemia and muscle atrophy are frequently found in patients with chronic kidney disease (CKD) and patients being treated by dialysis. These abnormalities are usually attributed to malnutrition, meaning that they are caused by an inadequate diet. However, the evidence indicates that malnutrition is rarely the mechanism causing loss of protein stores. Instead, low values of serum albumin are closely related to the presence of inflammation and loss of muscle mass is attributable to activation of specific proteases. In uremic rodents and patients, the initial step in the loss of muscle protein is an activation of caspase-3. This cleaves the complex structure of muscle, and its action can be detected by the presence of a characteristic 14-kDa actin fragment in the insoluble fraction of muscle. The second step in uremia-induced loss of muscle protein is an activation of the ubiquitin-proteasome system, which rapidly degrades proteins released by caspase-3 cleavage of muscle proteins. Activation of both caspase-3 and the ubiquitin-proteasome system occur when there is suppression of the cellular signaling pathway activated by insulin/insulinlike growth factor 1, the phosphatidylinositol 3-kinase/Akt pathway. A potential therapeutic target for preventing loss of muscle protein is to stimulate activity of this signaling pathway.

Alterations of protein metabolism in acromegaly

Growth hormone is a powerful anabolic hormone necessary for normal growth, but its importance in maintaining the cellular and protein mass in adult life is still unclear. However, it is viewed as a drug capable of combating the tissue loss and some metabolic derangements of aging. Growth hormone excess causes acromegaly, a disease characterized by overgrowth of some tissues and multiple metabolic abnormalities. The purpose of this article is to review recent knowledge in acromegaly considering it as a model for clarifying aspects of growth hormone action on body composition, protein dynamics and molecular mechanisms in adult life. Acromegaly induces well-documented changes in body fat (decreased), and bone density and water retention (increased), but there are less-clear changes in protein and body cell-mass accretion. Recent studies related insulin resistance to glucose metabolism to accelerated fat oxidation and described the reversibility of such alterations after surgical or pharmacologic therapy. Less attention was paid to changes in protein metabolism. Acromegalics are profoundly insulin-resistant to the antiproteolytic action of insulin, but amino acids are channelled towards protein synthesis because they are still normally spared from oxidation by insulin. This insulin resistance persists months after the surgical cure of acromegaly when glucose metabolism is already normalized. Recent studies suggested that increased use of fat for fuel by growth hormone may also promote protein anabolism and reduce amino acid oxidation. Despite important advances in understanding molecular mechanisms in acromegaly, the specific effects on body cell and protein mass and the specific modulation of local protein dynamics remain poorly defined.

Protein metabolism in guanethidine-treated rats.

The aim of the present study was to evaluate the effect of short-term adrenergic blockade on the rate of whole-body protein turnover and leucine oxidation, and on protein synthesis in specific tissues in male rats. Adrenergic blockade was induced by guanethidine (100 mg/kg body weight subcutaneously). The control group was treated with saline. On the second day, the parameters of whole-body protein and leucine metabolism were evaluated using a primed constant intravenous infusion of L-[1-(14)C]leucine. Protein synthesis in tissues was determined on the basis of L-[1-(14)C]leucine incorporation. Guanethidine treatment caused a decrease in norepinephrine in skeletal muscle. Whole-body leucine oxidation and leucine oxidized fraction were higher in guanethidine-treated rats. There was an insignificant effect of guanethidine on whole-body proteolysis, protein synthesis and leucine clearance. However, protein balance was negative due to the larger difference between protein synthesis and proteolysis in guanethidine-treated animals compared to controls. In guanethidine-treated rats, protein synthesis was higher in the gastrocnemius muscle and in the kidneys and lower in liver and spleen. Changes in the small intestine and colon were insignificant. In addition, a marked decrease in concentration of several amino acids has been observed in the liver, the kidneys and the spleen. It is concluded that adrenergic blockade induced by guanethidine is associated with significant changes in protein metabolism, leucine oxidation and amino acid concentrations in several tissues. The most important consequences of treatment are considered to be a negative effect on protein balance, increased protein turnover in skeletal muscle and kidneys and decreased protein synthesis in the liver and spleen. These changes may also be induced by administration of other sympathetic blocking agents, e.g. in treatment of hypertension.

Dietary restriction initiated late in life can restore age‐related changes in protein metabolism

Dietary restriction (DR) from weaning or young adult stages in laboratory animals throughout their usual life span extends maximum lifespan and retards the development of a broad spectrum of pathophysiological changes. However, the effects of DR when performed at middle age or later have not been well investigated. We previously reported that short‐term (about 2.5 months) DR in early senescence reduced the amount of altered proteins and shortened the half‐life of proteins. Furthermore, our previous studies in rats demonstrated DR initiated later in life reduces the content of oxidatively modified proteins, measured as protein carbonyls, in mitochondria from old rats. In addition, we recently found that the age‐related decline in the activities of proteasomes that have been implicated in removal of altered proteins was restored by DR. Thus, our findings suggest that DR initiated even relatively late in life can restore an animal's youthful condition, reducing the accumulation of altered proteins.

Protein metabolism in Spodoptera litura (F.) is influenced by the botanical insecticide azadirachtin

Azadirachtin, as a botanical insecticide, affects a wide variety of biological processes, including reduction of feeding, suspension of molting, death of larvae and pupae, and sterility of emerged adults in a dose-dependent manner. However, the mode of action of this toxin remains obscure. By using proteomic techniques, we analyzed changes in protein metabolism of Spodoptera litura (F.) induced by azadirachtin. Following feeding 4th instar larvae of S podoptera litura (F.) with an artificial diet containing 1 ppm azadirachtin until pupation, 48 h old pupae were collected and protein samples prepared. Total soluble protein content was measured and the results showed that azadirachtin significantly influenced protein level. Moreover, the proteins were separated by 2-DE (two-dimensional polyacrylamide gel electrophoresis) and 10 proteins were significantly affected by azadirachtin treatment when compared to an untreated control. Six of these proteins were identified with peptide mass fingerprinting using MALDI-TOF-MS after in-gel trypsin digestion. These proteins are involved in various cellular functions. One identified protein may function as an ecdysone receptor, which regulates insect development, and reproduction. It is suggested that the botanical insecticide azadirachtin affects protein expression and the azadirachtin-related proteins would be essential for a better understanding of the mechanisms by which neem toxins exert their effects on insects.

Restoration of Protein Synthesis in Heart and Skeletal Muscle After Withdrawal of Alcohol

The rate of protein synthesis is diminished after chronic alcohol consumption through changes in both mRNA translation initiation and elongation. It remains unknown how long adverse effects of alcohol on protein synthesis persist after withdrawal from ethanol. We examined the effect of removal of alcohol from the diet of rats for 72 hr after chronic alcohol exposure (16 weeks) on rates of protein synthesis and potential mechanisms for controlling mRNA translation in heart, skeletal muscle, and liver. Rates of protein synthesis were measured after intravenous infusion of [3H]-l-phenylalanine. The formation of active eukaryotic initiation factor (eIF)4E.eIF4G complex, the cellular content of eukaryotic elongation factor (eEF)1A and eEF2, and the phosphorylation state of eEF2 and S6K1 were measured in each tissue. Withdrawal of alcohol from the diet restored protein synthesis in heart and skeletal muscle to values obtained in pair-fed control rats not exposed to alcohol. However, the organ weight and protein content per muscle was not affected by withdrawal of alcohol from the diet. In both heart and skeletal muscle, the restoration of protein synthesis correlated with reversal of defects in the formation of active eIF4E.eIF4G complex and eEF1A content. Myocardial eEF2 content was also restored to control values after withdrawal of alcohol from the diet. In the gastrocnemius, there was a decrease in the cellular content of eEF2. The lower eIF2 content may have been counterbalanced by an increased activity of eEF2 through a reduction in the phosphorylation state of eEF2 allowing protein synthesis to proceed unimpeded. These studies indicate that changes in protein metabolism observed during chronic alcohol intake are reversible and do not, at this stage, represent an irreversible change in cardiac or skeletal muscle.

Short- and long-term effects of growth hormone (GH) replacement on protein metabolism in GH-deficient adults.

Reduced fat-free mass (FFM) in GH-deficient (GHD) adults is improved by GH replacement, but the protein metabolic changes are unclear. Using iv [(2)H(3)]leucine and oral l-[(13)C(1)]leucine infusions and dual emission x-ray absorptiometry, we compared leucine kinetics and body composition in eight GHD adults and eight healthy controls in the fasted and fed states, before and after 2 wk and 6 months of GH replacement. Leucine kinetics were not different between pretreatment GHD subjects and controls. After 2 wk of GH treatment, leucine oxidation decreased in the GHD subjects compared with baseline values [fasted, 41 +/- 6 vs. 30 +/- 5 micromol/kg FFM.h (P < 0.01); fed, 49 +/- 3 vs. 41 +/- 3.6 micromol/kg FFM.h (P < 0.05)], leucine balance improved [fasted, -14 +/- 4 vs. -3.5 +/- 3 micromol/kg FFM.h (P < 0.01); fed, 65 +/- 10 vs. 72 +/- 7 micromol/kg FFM.h (P = 0.07)], and protein synthesis increased [fasted, 116 +/- 5 vs. 131 +/- 6 micromol/kg FFM.h (P < 0.05); fed, 103 +/- 6 vs. 116 +/- 6 micromol/kg FFM.h (P < 0.05)]. After 6 months of GH treatment, these changes were not maintained in the fed state. The five GHD subjects with decreased FFM at baseline showed a significant increase after 6 months of GH treatment (P < 0.05). GH replacement in GHD acutely improves protein balance by stimulating synthesis and inhibiting catabolism. After 6 months, protein kinetics reached a new homeostasis to maintain the net gain in FFM.

Frailty amplifies the effects of aging on protein metabolism: role of protein intake

We previously showed that muscle contributes less to whole-body protein breakdown with healthy aging. We hypothesized that frailty further compromises protein metabolism and that short-term protein supplementation improves protein status. Protein metabolism was studied with the oral, 60-h [(15)N]glycine and N(tau)-methylhistidine methods in 8 frail and 13 healthy elderly women during a 9-d isoenergetic, isonitrogenous formula diet and then after increased protein intakes in the frail women, to match the intakes of healthy subjects, for 12 d. Compared with healthy women, frail women had higher rates of whole-body protein synthesis and breakdown per kg fat-free mass and lower rates of muscle protein breakdown when expressed as total amounts per day but higher rates when expressed per kg muscle. Because muscle mass was lower in frail women, the contribution of muscle to whole-body protein breakdown was lower and that of nonmuscle lean tissues was higher. The protein-enriched diet had no effect on these variables but resulted in an increase in net endogenous protein balance and a positive nitrogen balance at the end of the diet period. Frailty exacerbates age-related changes in protein metabolism by inducing an increase in muscle protein catabolism and a decrease in muscle mass. At low protein intakes, the increase in muscle catabolism may be a form of protection for both nonmuscle lean tissue mass and function at the expense of muscle mass. Frail women maintained the capacity to retain nitrogen after increased protein intakes, which could convey health benefits if sustained over a long enough period to result in lean tissue accretion.

Effect of acute acidosis on protein and amino acid metabolism in rats

Background & aims: Metabolic acidosis is a common finding in critical illness. The aim of the present study was to evaluate acute acidosis as a signal that induces changes in protein metabolism. Methods: In the first study, Wistar rats were infused for 6 h with HCl or saline resulting in blood pH 7.30±0.03 and 7.46±0.02, respectively. The whole body protein metabolism was evaluated using l-[1- 14C]leucine. In the second study, soleus and extensor digitorum longus muscles from normal rats were incubated in medium, pH 7.4, 7.3 or 7.0. Protein metabolism was evaluated using l-[1- 14C]leucine and tyrosine release. Results: In the in vivo study we observed increased protein turnover–protein synthesis, proteolysis and leucine oxidation and more negative protein balance in rats with acidosis. There was no change in protein synthesis in gastrocnemius muscle. We observed an increase in plasma levels of most amino acids including branched-chain amino acids and a decrease in intracellular amino acid pool in skeletal muscle. In vitro decrease in pH of 0.1 had no effect on protein metabolism, decrease of 0.4 decreased protein turnover and leucine oxidation. Conclusion: Acute metabolic acidosis is a protein wasting condition. Direct effect of acidosis on skeletal muscle is under condition in vivo modified by neurohumoral regulations.

Nitrogen balance of healthy Dutch women before and during pregnancy

Experimental studies including longitudinal nitrogen balance studies could provide insight into protein metabolism in pregnancy. Our aim was to determine the development of nitrogen balance during pregnancy compared with nitrogen balance before pregnancy in women consuming imposed constant diets. We also tracked changes in muscle mass and lean body mass by measuring urinary 3-methylhistidine (3-MeH) and urinary creatinine. Nitrogen balance was determined over 8 d in 12 healthy Dutch women before pregnancy and at weeks 12, 23, and 34 of gestation. Complete daily diets were supplied during each balance period so that each subject's energy, protein, and macronutrient intakes were similar in amount and composition in all 4 balance periods. Throughout pregnancy there was no significant change in loss of nitrogen in feces and therefore no change in protein digestibility. The amount of nitrogen excreted in urine in late pregnancy (11.0 +/- 1.4 g/d) was significantly (P < 0.01) less than in early pregnancy (12.6 +/- 1.3 g/d). Nitrogen retention increased toward term, even though energy balance became progressively negative. The difference between the first (-0.4 +/- 1.7 g N/d) and third (1.2 +/- 1.6 g N/d) trimester was significant (P < 0.05). No differences were found in either 3-MeH or creatinine excretion between trimesters. These urinary nitrogen excretion and nitrogen retention data show that when the dietary supply remains constant, nitrogen balance increases toward the end of pregnancy, suggesting a more efficient use of dietary protein later in pregnancy. Urinary 3-MeH and creatinine excretion indicated no change in protein metabolism.

Alleviation of Changes in Protein Metabolism in NaCl-Stressed Wheat Seedlings by Thiamine

NaCl-stress induced a pronounced suppression in growth of wheat seedlings. The most abundant amino acids (cysteine, arginine, methionine) constituting about 55 % of total free amino acid content in control wheat were reduced in 100 mM NaCl-treated plants. However, valine, isoleucine, aspartic acid and proline accumulated in response to NaCl stress and NaCl-treated wheat seedlings showed 1.6 fold increase in total free amino acids compared to the control. Addition of 2 [micro ]M thiamine alleviated the effects of NaCl on the amino acid composition and the amount of total free amino acids decreased to that in the control. Content of 26 kDa protein increased in NaCl-treated plants, stimulation was more pronounced in roots than in shoots. In contrast, the contents of 13 and 20 kDa proteins decreased. After addition of thiamine, the 24 kDa protein, which disappeared with NaCl treatment, has been initiated again. Moreover, thiamine treatment stimulated the accumulation of the 20 kDa protein.

Exercise Affects Protein Utilization in Healthy Children

Although health initiatives promote increased physical activity in children, the physiologic outcomes have not been well characterized. This investigation examined the effects of programmed aerobic exercise on protein metabolism in children (n = 7; mean +/- SEM: 9.14 +/- 0.46 y old; weight, 32.1 +/- 1.6 kg; height, 138 +/- 2.5 cm; and body mass index, 16.21 +/- 0.36 kg/m(2) ) using (15)N-glycine methodology. Boys (n = 5) and girls (n = 2) walked (5 d/wk, 3.2-6.4 km/d) for 6 wk. Criterion measures taken at baseline (Pre) and after the exercise program (Post) included anthropometric data, dietary assessment, nitrogen balance, nitrogen flux (Q), protein synthesis (PS), protein breakdown (PB) and net protein balance [(Net) = PS - PB]. After the walking program, there were no significant changes in body weight, fat-free mass or percentage of body fat, whereas height increased (P < 0.01). Energy and protein intakes were constant throughout the study. Nitrogen balance was significantly more positive Post than Pre (P < 0.05). There was a significant decrease in Q (P < 0.0001) with corresponding decreases in PS (P < 0.001) and PB (P < 0.01). These data provide the first evidence that programmed aerobic exercise alters whole-body protein utilization in healthy, nonobese children. Longitudinal studies are required to further examine changes in protein metabolism associated with increased physical activity in this population. In addition, findings suggest a need to evaluate nutrient requirements for healthy, physically active boys and girls.

Muscle fibre growth in undernourished reindeer calves ( Rangifer tarandus tarandus L.) during winter

To study whether moderate under-nutrition causes muscle wasting, reindeer ( Rangifer tarandus tarandus L.) calves were fed either pelleted reindeer feed ad libitum ( n=8) or restricted amounts of lichens ( n=8). The restricted amount was 60% of ad libitum intake of lichens, and the feeding period was 6 weeks preceded by a 2-week adjustment period. Biopsy samples from the middle gluteal muscle ( M. gluteus medius) for the analysis of fibre composition and area, as well as for the activity of cathepsin B were taken before the restriction period in November and January, and after the restriction period in April. In all calves the muscle fibre composition remained unchanged during the winter. In the lichen group, the fibre size also remained unchanged, whereas in control calves the cross sectional area of type I and type IIA fibres increased significantly from November to April. Cathepsin B activity decreased in all calves from November to January and remained at that low level for the rest of the study period, which suggests an attenuated rate of protein degradation. These results can be taken as an indication that moderate under-nutrition causes no muscle wasting in reindeer calves, and the decreased availability of nitrogen is partially compensated for by adaptive decrease in protein degradation. Interestingly the adaptive changes in protein metabolism are equally well seen in the well-fed controls as in the undernourished lichen-fed reindeer.

Stress Responses and Changes in Protein Metabolism in Carp Cyprinus carpio during Cadmium Exposure

Stress responses and changes in protein metabolism were studied in common carp Cyprinus carpio exposed to 0, 0.8, 4, and 20 μM cadmium (Cd) over a 29-day period. Blood and other tissue samples were taken after 4 and 29 days of exposure. The highest Cd concentration proved to be lethal to the fish, resulting in 100% mortality after 21 days of exposure. Cd accumulated in the tissues in the following order: kidney>liver>gills. Blood hematocrit, blood hemoglobin, plasma glucose, plasma lactate, and tissue total protein contents were not significantly altered. The concentrations of Cd and zinc (Zn) binding metallothioneins ((Cd, Zn)-MTs) were in the following order=liver>kidney>gills. An increase in (Cd, Zn)-MTs was observed at all exposure concentrations at days 4 and 29 in kidney and at Day 29 in gills. No significant changes in (Cd, Zn)-MT contents were found in liver. The concentrations of free amino acids and the activities of proteases were increased at Day 4 in gills, liver, and kidney of carp exposed to 4 and 20 μM Cd, and in gills and kidney at Day 29 in carp exposed to 4 μM Cd. The observed increases in the activities of aspartate aminotransferase and alanine aminotransferase suggest that the observed proteolysis is intended to increase the role of proteins in the energy production during Cd stress. However, this increased activity of both aminotransferases was not found in gills during exposure to the lethal Cd concentration, indicating that Cd may also cause an inhibitory effect on the activity of these enzymes above a certain level.

Differential Insulin Sensitivities of Glucose, Amino Acid, and Albumin Metabolism in Elderly Men and Women

Regulation of glucose homeostasis by insulin is modified during aging, but whether this alteration is associated with changes in protein metabolism is less defined. Insulin dose responses of whole body glucose, leucine, and albumin metabolism have been investigated using isotopic dilution of d-[6, 6-2H2]glucose and l-[1-13C]leucine in 14 young (Y; 24.0 ± 0.9 yr; mean ± sem, 20.5 ± 0.4 kg/m2) and 12 healthy elderly subjects (E; 69.4 ± 0.6 yr; 24.6 ± 0.8 kg/m2) using a euglycemic and euaminoacidemic hyperinsulinemic clamp at two insulin infusion rates of 0.2 and 0.5 mU/kg·min (CL1 and CL2, respectively). Despite significantly higher plasma insulin in E than in Y, the glucose disposal rate was lower in E than in Y at both insulin levels, whereas glucose production was normally suppressed. Whole body protein breakdown was less inhibited by insulin in E than in Y at CL1 (−13.5 ± 1.4% vs. −8.8 ± 1.3%, Y vs. E, P < 0.05), but not significantly at CL2 (−22.0 ± 1.4% vs.− 18.8 ± 1.7%, Y vs. E, P = NS). The albumin synthesis rate was identical and stimulated to the same extent by insulin in groups Y and E. Gender affected basal leucine metabolism, but the response to insulin was similar in both groups. In conclusion, decreased insulin action on glucose disposal is associated with a reduced insulin sensitivity for protein breakdown in healthy elderly subjects at low insulin concentrations. Higher insulin levels compensate for a reduced insulin action on protein metabolism in elderly subjects.