Showing papers in "American Journal of Physiology-endocrinology and Metabolism in 1995"
TL;DR: Results indicate that, during recovery after resistance exercise, muscle protein turnover is increased because of an acceleration of synthesis and degradation and a postexercise acceleration of amino acid transport may contribute to the relatively greater stimulation of protein synthesis.
Abstract: The rates of protein synthesis and degradation and of amino acid transport were determined in the leg muscle of untrained postabsorptive normal volunteers at rest and approximately 3 h after a resistance exercise routine. The methodology involved use of stable isotopic tracers of amino acids, arteriovenous catheterization of the femoral vessels, and biopsy of the vastus lateralis muscle. During postexercise recovery, the rate of intramuscular phenylalanine utilization for protein synthesis increased above the basal value by 108 +/- 18%, whereas the rate of release from proteolysis increased by 51 +/- 17%. Muscle protein balance improved (P < 0.05) after exercise but did not become positive (from -15 +/- 12 to -6 +/- 3 nmol phenylalanine.min-1.100 ml leg volume-1). After exercise, rates of inward transport of leucine, lysine, and alanine increased (P < 0.05) above the basal state from 132 +/- 16 to 208 +/- 29, from 122 +/- 8 to 260 +/- 8, and from 384 +/- 71 to 602 +/- 89 nmol.min-1.100 ml leg-1, respectively. Transport of phenylalanine did not change significantly. These results indicate that, during recovery after resistance exercise, muscle protein turnover is increased because of an acceleration of synthesis and degradation. A postexercise acceleration of amino acid transport may contribute to the relatively greater stimulation of protein synthesis.
715 citations
TL;DR: It is concluded that increasing testosterone concentrations in elderly men increases skeletal muscle protein synthesis and strength, and this increase may be mediated by stimulation of the intramuscular IGF-I system.
Abstract: Aging men develop a significant loss of muscle strength that occurs in conjunction with a decline in serum testosterone concentrations. We investigated the effects of testosterone administration to six healthy men [67 +/- 2 (SE) yr] on skeletal muscle protein synthesis, strength, and the intramuscular insulin-like growth factor I (IGF-I) system. Elderly men with serum testosterone concentrations of 480 ng/dl or less were given testosterone injections for 4 wk to produce serum concentrations equal to those of younger men. During testosterone administration muscle strength (isokinetic dynamometer) increased in both right and left hamstring and quadricep muscles as did the fractional synthetic rate of muscle protein (stable-isotope infusion). Ribonuclease protection assays done on total RNA from muscle showed that testosterone administration increased mRNA concentrations of IGF-I and decreased mRNA concentrations of insulin-like growth factor binding protein-4. We conclude that increasing testosterone concentrations in elderly men increases skeletal muscle protein synthesis and strength. This increase may be mediated by stimulation of the intramuscular IGF-I system.
596 citations
TL;DR: Physiological hyperinsulinemia acutely reduces urinary UA and Na excretion in a coupled fashion and was associated with a 30% fall in urine Na excrete.
Abstract: Although hyperuricemia is a frequent finding in insulin-resistant states, insulin's effect on renal uric acid (UA) handling is not known. In 20 healthy volunteers, diastolic blood pressure, body we...
417 citations
TL;DR: It is suggested that relatively large strains alone are not sufficient to activate bone cells, and high strain rates and possibly stress-generated fluid flow are required to stimulate new bone formation.
Abstract: Bone tissue can detect and respond to its mechanical environment, but there is no consensus for how bone cells detect mechanical loads. Some think that cells sense tissue deformation (strain) and respond when strain is abnormally high. However, strains in bone tissue are usually very small, and it is questionable whether bone cells are sensitive enough to detect them. Another theory suggests that mechanical loads are coupled to the bone cells by stress-generated fluid flow within the bone tissue, which is dependent on the rate of change of bone strain. We applied bending loads to the tibiae of adult rats to create equivalent peak strains in the bone tissue but with varied rates of strain. Bone formation was significantly increased in the two experimental groups when the highest strain rates were compared with lower strain rates (P < 0.01), and the amount of new bone formation was directly proportional to the rate of strain in the bone tissue. These results suggest that relatively large strains alone are not sufficient to activate bone cells. High strain rates and possibly stress-generated fluid flow are required to stimulate new bone formation.
364 citations
TL;DR: Data do not support an independent relationship between fiber type and insulin action in obesity, but a reduced skeletal muscle type I fiber population may be one component of a multifactorial process involved in the development of insulin resistance.
Abstract: The purpose of this study was to determine if a relationship exists among skeletal muscle fiber composition, adiposity, and in vitro muscle glucose transport rate in humans. Rectus abdominus muscle...
300 citations
TL;DR: The model-derived rate of protein synthesis was highly correlated with the same value calculated by means of the tracer incorporation technique and amino acid transport rates were in the range expected from literature values.
Abstract: We have used stable isotopic tracers of amino acids to measure in vivo transmembrane transport of phenylalanine, leucine, lysine, alanine, and glutamine as well as the rates of intracellular amino acid appearance from proteolysis, de novo synthesis, and disappearance to protein synthesis in human skeletal muscle. Calculations were based on data obtained by the arteriovenous catheterization of the femoral vessels and muscle biopsy. We found that the fractional contribution of transport from the bloodstream to the total intracellular amino acid appearance depends on the individual amino acid, varying between 0.63 +/- 0.02 for phenylalanine and 0.22 +/- 0.02 for alanine. Rates of alanine and glutamine de novo synthesis were approximately eight and five times their rate of appearance from protein breakdown, respectively. The model-derived rate of protein synthesis was highly correlated with the same value calculated by means of the tracer incorporation technique. Furthermore, amino acid transport rates were in the range expected from literature values. Consequently, we conclude that our new model provides a valid means of quantifying the important aspects of protein synthesis, breakdown, and amino acid transport in human subjects.
291 citations
TL;DR: The findings suggest that accelerated muscle proteolysis and muscle wasting in tumor-bearing rats result primarily from activation of the ATP-dependent pathway involving ubiquitin and the proteasome.
Abstract: Rats implanted with Yoshida ascites hepatoma (YAH) show a rapid and selective loss of muscle protein due mainly to a marked increase (63-95%) in the rate of protein degradation (compared with rates in muscles of pair-fed controls). To define which proteolytic pathways contribute to this increase, epitrochlearis muscles from YAH-bearing and control rats were incubated under conditions that modify different proteolytic systems. Overall proteolysis in either group of rats was not affected by removal of Ca2+ or by blocking the Ca(2+)-dependent proteolytic system. Inhibition of lysosomal function with methylamine reduced proteolysis (-12%) in muscles from YAH-bearing rats, but not in muscles of pair-fed rats. When ATP production was also inhibited, the remaining accelerated proteolysis in muscles of tumor-bearing rats fell to control levels. Muscles of YAH-bearing rats showed increased levels of ubiquitin-conjugated proteins and a 27-kDa proteasome subunit in Western blot analysis. Levels of mRNA encoding components of proteolytic systems were quantitated using Northern hybridization analysis. Although their total RNA content decreased 20-38%, pale muscles of YAH-bearing rats showed increased levels of ubiquitin mRNA (590-880%) and mRNA for multiple subunits of the proteasome (100-215%). Liver, kidney, heart, and brain showed no weight loss and no change in these mRNA species. Muscles of YAH-bearing rats also showed small increases (30-40%) in mRNA for cathepsins B and D, but not for calpain I or heat shock protein 70. Our findings suggest that accelerated muscle proteolysis and muscle wasting in tumor-bearing rats result primarily from activation of the ATP-dependent pathway involving ubiquitin and the proteasome.
263 citations
TL;DR: It is demonstrated that rhIL-6 induces many of the endocrinologic and metabolic changes found in catabolic states and thus may mediate some of the metabolic effects previously ascribed to other cytokines.
Abstract: Interleukin-6 (IL-6) is one of the major circulating cytokines in catabolic states. To investigate its endocrinologic and metabolic actions in vivo, we studied eight patients with metastatic renal ...
254 citations
TL;DR: It is concluded that the myocardial fibrosis observed in response to chronic mineralocorticoid elevation and salt loading is a humorally mediated event independent of hypokalemia, hypertension, and cardiac hypertrophy.
Abstract: Uninephrectomized rats maintained on 1.0% NaCl to drink and infused with aldosterone (0.75 microgram/h) for 8 wk have previously been shown to develop hypertension, cardiac hypertrophy, and cardiac fibrosis. In the present study we have shown that K+ supplementation (1.0% NaCl plus 0.4% KCl drinking solution) alters neither the interstitial nor the perivascular fibrotic response to mineralocorticoid treatment. Second, rats receiving 0.75 microgram/h 9 alpha-fluorocortisol, a mineralocorticoid and glucocorticoid agonist, respond with hypertension and cardiac fibrosis without cardiac hypertrophy. Finally, intracerebroventricular infusion of the mineralocorticoid receptor antagonist RU-28318 blocks blood pressure elevation, but not cardiac hypertrophy or fibrosis, when aldosterone is coinfused peripherally. We conclude that the myocardial fibrosis observed in response to chronic mineralocorticoid elevation and salt loading is a humorally mediated event independent of hypokalemia, hypertension, and cardiac hypertrophy. It remains to be determined whether the fibrosis observed in the presence of excess salt represents a direct (e.g., cardiac) effect of mineralocorticoid hormones or one mediated via a primary action on classical epithelial aldosterone target tissues (e.g., kidney).
243 citations
TL;DR: It is suggested that resistance exercise training improved muscle strength and anabolism in older men, but these improvements were not enhanced when exercise was combined with daily GH administration.
Abstract: The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle protein anabolism associated with heavy-resistance exercise training in older men. Twenty-three healthy, sedentary men (67 +/- 1 yr) with low serum insulin-like growth factor I levels followed a 16-wk progressive resistance exercise program (75-90% max strength, 4 days/wk) after random assignment to either a GH (12.5-24 micrograms.kg-1.day-1; n = 8) or placebo (n = 15) group. Fat-free mass (FFM) and total body water increased more in the GH group. Whole body protein synthesis and breakdown rates increased in the GH group after treatment. However, increments in vastus lateralis muscle protein synthesis rate, urinary creatinine excretion, and training-specific isotonic and isokinetic muscle strength were similar in both groups, while 24-h urinary 3-methylhistidine excretion was unchanged after treatment. These observations suggest that resistance exercise training improved muscle strength and anabolism in older men, but these improvements were not enhanced when exercise was combined with daily GH administration. The greater increase in FFM with GH treatment may have been due to an increase in noncontractile protein and fluid retention.
241 citations
TL;DR: Its production before the increase in transcription of matrix protein mRNA, and before the transcription of IGF-I mRNA in bone surface cells, represents persuasive evidence for a role for osteocytes, and for IGF- I, in the osteogenic response of bone to mechanical stimulation.
Abstract: We recently developed an experimental model whereby a single 10-min episode of mechanical stimulation induces bone formation in the eighth caudal vertebra of 13-wk-old rats. We used this model to r...
TL;DR: Fasting and glucose-stimulated insulin responses were greater in obese than in nonobese adolescents, who, in turn, had greater responses than lean women, and visceral fat, but neither waist-to-hip circumference ratio nor subcutaneous fat, was highly correlated with basal insulin secretion.
Abstract: To establish whether alterations in insulin action and secretion and their relationship to body fat distribution occur early in the course of developing obesity, we studied 14 obese adolescent girls [13.2 +/- 0.7 yr, body mass index (BMI) 32 +/- 1.4], 16 nonobese young women (24.0 +/- 0.6 yr, BMI 21.0 +/- 0.9). Insulin action was assessed by a sequential two-step (8 and 40 mU,m-2.min-1) euglycemic insulin clamp in combination with [1-13C]glucose and indirect calorimetry. Insulin secretion was determined by the hyperglycemic clamp technique (6.9 mmol/l). Magnetic resonance imaging was used to quantify visceral and subcutaneous abdominal fat depots. In obese girls, an impairment in glucose disposal was present with both insulin doses; at the higher dose, rates of glucose uptake were reduced by 30% in nonobese girls (240 +/- 30 vs. 340 +/- 19 mg.m-2.min-1, P < 0.05) and by an additional 29% (170 +/- 17 mg.m-2.min-1, P < 0.05) in obese girls. Insulin infusion failed to stimulate glucose oxidation and to suppress lipid oxidation only in obese girls. Suppression of free fatty acid levels, but not hepatic glucose production, was decreased in obese girls compared with controls. Fasting and glucose-stimulated insulin responses were greater in obese than in nonobese adolescents, who, in turn, had greater responses than lean women. In obese girls, visceral fat, but neither waist-to-hip circumference ratio nor subcutaneous fat, was highly correlated with basal insulin secretion (r = 0.89, P < 0.001), stimulated insulin secretion (r = 0.61, P < 0.05), and insulin resistance (r = -0.87, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The data suggest that the slower myofibrillar synthesis rate in older subjects cannot be explained by disuse, and whole body protein turnover increased only in the younger group, and 24-h urinary 3-methylhistidine excretion was not significantly affected by training.
Abstract: Muscle protein synthesis is slower in healthy older men and women than in young adults, but whether this results from relative disuse rather than aging is unclear. The present study was done to examine rates of myofibrillar protein synthesis before and after a 3-mo progressive resistance exercise program in young and old men and women. Protein synthesis was determined by incorporation of the tracer L-[1-13C]leucine into myofibrillar proteins obtained from the vastus lateralis muscle by needle biopsy. Before exercise, mean fractional myofibrillar synthesis was 33% slower (P < 0.01) in nine older subjects (62-72 yr old, 5 men and 4 women) than in 9 young subjects (22-31 yr old, 5 men and 4 women). Initial strength, as determined by three-repetition-maximum tests, was significantly less in the older group. Strength and training weights increased similarly in young and old groups, when expressed in relation to baseline values. Posttraining myofibrillar synthesis was determined on the day after the final training session. There was not a significant change in fractional myofibrillar synthesis in either the young or the old group after training, and the rate in the older group remained 27% slower (P < 0.05). Whole body protein turnover increased approximately 10% only in the younger group, and 24-h urinary 3-methylhistidine excretion (an index of myofibrillar proteolysis) was not significantly affected by training. These data suggest that the slower myofibrillar synthesis rate in older subjects cannot be explained by disuse.
TL;DR: Hypercortisolemia increases metabolic rate and may be in part responsible for the hypermetabolic state in injury, as measured by increases in leucine and phenylalanine appearance rates and glutamine flux.
Abstract: Hydrocortisone was infused overnight into nine normal healthy adults on three occasions at 0, 80, and 200 micrograms.kg-1.h-1, producing plasma cortisol concentrations of 10.6 +/- 1.2, 34.0 +/- 2.0, and 64.9 +/- 4.3 micrograms/dl, respectively. L-[1-13C]leucine, L-[phenyl-2H5]phenylalanine, and L-[2-15N]glutamine were infused during the last 7 h of hypercortisolemia to measure amino acid kinetics. During the last 3.5 h, somatostatin, glucagon, and insulin were infused to reduce the cortisol-induced elevation in plasma insulin to basal. Hypercortisolemia increased plasma glucose, free fatty acid (FFA), and insulin concentrations. Institution of the somatostatin clamp returned insulin to basal but increased glucose and FFA. Acute hypercortisolemia increased protein breakdown 5-20%, as measured by increases in leucine and phenylalanine appearance rates. Normalizing insulin during hypercortisolemia did not alter phenylalanine flux but enhanced leucine appearance rate, the latter result indicating that insulin was affecting leucine metabolism during hypercortisolemia. The fraction of the leucine flux that was oxidized was not significantly increased with hypercortisolemia, but disposal by the nonoxidative route of leucine uptake for protein synthesis was increased. Hypercortisolemia increased cycling of amino acids by increasing protein breakdown and synthesis, but the increase in this process could have increased resting energy expenditure (REE) only 1-2%. Hypercortisolemia increased glutamine flux in a dose-dependent fashion through an increase in de novo synthesis, which presumably reflects increased release from skeletal muscle. Hypercortisolemia increased REE 9-15% at the 80 and 200 micrograms.kg-1.h-1 infusion rates. Respiratory quotient did not rise with cortisol infusion but tended to decrease, suggesting that the increase in REE was fueled by increased oxidation of fat. These data demonstrate that hypercortisolemia increases metabolic rate and may be in part responsible for the hypermetabolic state in injury.
TL;DR: Large increases in cathepsins B and L and dipeptidyl aminopeptidase I activities during stretch, with or without stimulation, suggest a role for these enzymes in tissue remodeling during muscle hypertrophy.
Abstract: The relative merits of the separate and combined uses of stretch and electrical stimulation at 10 Hz in influencing the rates of protein synthesis in vivo, proteolysis, and the growth of the extensor digitorum longus muscle have been investigated after 3 days in the rabbit. Continuous electrical stimulation failed to change muscle protein turnover or growth. Static stretch caused significant adaptive growth, with increases in c-fos, c-jun, and insulin-like growth factor I (IGF-I; 12-fold) mRNA levels, and protein (19%), RNA (128%), and DNA (45%) contents. Both the fractional (138%) and total (191%) rates of protein synthesis increased with stretch, correlating with increased ribosomal capacities. Combining stretch and electrical stimulation increased the mRNA concentration of IGF-I (40-fold). The adaptive growth was greater (35%), with massive increases in the nucleic acids (185 and 300%), ribosomal capacities (230%), and the rates of protein synthesis (345 and 450%). Large increases (i.e., 200-400%) in cathepsins B and L and dipeptidyl aminopeptidase I activities during stretch, with or without stimulation, suggest a role for these enzymes in tissue remodeling during muscle hypertrophy.
TL;DR: It is concluded that use of the acetate correction factor in place of the bicarbonate Correction factor should improve the accuracy of isotopic measurements of plasma fatty acid oxidation, because it accounts for label fixation that might occur at any step between the entrance of labeled acetyl-CoA into the tricarboxylic acid cycle until the recovery of label in breath CO2.
Abstract: The purpose of this study was to acquire a new correction factor for use in tracer estimations of plasma fatty acid oxidation that would fully account for label fixation during the infusion of fatty acid tracers. Thus volunteers were infused with 13C-labeled fatty acids and [1-14C]acetate in the basal state, during hyperinsulinemia-hyperglycemia (clamp), and during 1 h of cycling exercise. The fractional recovery of acetate label (i.e., the acetate correction factor) was 0.56 +/- 0.02, 0.50 +/- 0.03, and 0.80 +/- 0.03 in the basal state and during the clamp and exercise, respectively. Isotopically determined plasma fatty acid oxidation rates (mumol.kg-1.min-1) were 1.7 +/- 0.2, 0.8 +/- 0.2, and 6.4 +/- 0.5 (no correction); 2.1 +/- 0.2, 1.0 +/- 0.2, and 6.7 +/- 0.5 (bicarbonate correction); and 3.1 +/- 0.2, 1.5 +/- 0.2, and 8.2 +/- 0.4 (acetate correction). We conclude that use of the acetate correction factor in place of the bicarbonate correction factor should improve the accuracy of isotopic measurements of plasma fatty acid oxidation, because it accounts for label fixation that might occur at any step between the entrance of labeled acetyl-CoA into the tricarboxylic acid cycle until the recovery of label in breath CO2.
TL;DR: The existence of an exercise stimulus intrinsic to skeletal muscle, which raises LPL activity in part by pretranslational mechanisms, is suggested, a process that contributes to the improvement in circulating lipids seen with physical activity.
Abstract: Lipoprotein lipase (LPL) is regulated by exercise in humans, but the effects of exercise on LPL expression in different tissues and the molecular mechanisms involved are unclear. We assessed the ef...
TL;DR: The magnitude of coffee-induced thermogenesis and the influence of coffee ingestion on substrate oxidation were investigated in 10 lean and 10 obese women, over two 24-h periods in a respiratory chamber.
Abstract: The magnitude of coffee-induced thermogenesis and the influence of coffee ingestion on substrate oxidation were investigated in 10 lean and 10 obese women, over two 24-h periods in a respiratory ch...
TL;DR: The time between intravenous injection of a glucose bolus and the time the glucose concentration peaked in the subcutaneous tissue was measured in pentobarbital-anesthetized rats with implanted 290-microns-diameter amperometric sensors, consistent with dilution of the bolus in the cardiovascular system and transport of glucose by both diffusion and facilitated transport via a saturable mediator.
Abstract: The time between intravenous injection of a glucose bolus and the time the glucose concentration peaked in the subcutaneous tissue was measured in pentobarbital-anesthetized rats with implanted 290-microns-diameter amperometric sensors. Boluses of 100, 200, and 400 mg/kg body wt were injected. The glucose concentration in the jugular vein was monitored by frequent withdrawal and analysis of samples. The glucose concentration in the subcutaneous tissue was continuously monitored with the sensors. The times required for the subcutaneously implanted sensor to reach its maximum current, corrected for sensor response times, were 7.5 +/- 3.9, 9.8 +/- 5.5, and 10.0 +/- 4.4 min for the smallest to the largest dose, respectively. The shorter delay in response to the smallest dose was statistically significant (P < 0.03). The results were consistent with dilution of the bolus in the cardiovascular system and transport of glucose by both diffusion and facilitated transport via a saturable mediator. An understanding of the differences in the dynamics of venous vs. subcutaneous response to a glucose dose is important in developing algorithms for the control of blood glucose based on a subcutaneous measurement.
TL;DR: Although contractile activity increases insulin sensitivity and responsiveness in skeletal muscle, contraction causes a paradoxical decrease in insulin-stimulated tyrosine phosphorylation and PI 3-kinase activity.
Abstract: Insulin stimulates signaling reactions that include insulin receptor autophosphorylation and tyrosine kinase activation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and phosphatidylinositol 3-kinase (PI 3-kinase) activation. Muscle contraction has metabolic effects similar to insulin, and contraction can increase insulin sensitivity, but little is known about the molecular signals that mediate the effects of contraction. To investigate the effects of muscle contraction on insulin signaling, rats were studied after contraction of hindlimb muscles by electrical stimulation, maximal insulin injection in the absence of contraction, or contraction followed by insulin injection. Insulin increased tyrosine phosphorylation of the insulin receptor and IRS-1, whereas contraction alone had no effect. Contraction before insulin injection decreased the insulin effect on receptor and IRS-1 phosphorylation by 20-25%. Increased tyrosine phosphorylation of other proteins by insulin and/or contraction was not observed. Contraction alone had little effect on PI 3-kinase activity, but contraction markedly blunted the insulin-stimulated activation of IRS-1 and insulin receptor-immunoprecipitable PI 3-kinase. In conclusion, skeletal muscle contractile activity does not result in tyrosine phosphorylation of molecules involved in the initial steps of insulin signaling. Although contractile activity increases insulin sensitivity and responsiveness in skeletal muscle, contraction causes a paradoxical decrease in insulin-stimulated tyrosine phosphorylation and PI 3-kinase activity.
TL;DR: The data show that the efficiency of N retention and protein utilization during RT is higher in older subjects who consume 0.8 vs. 1.kg-1.day-1 dietary protein.
Abstract: Nitrogen (N) balance, fed-state leucine kinetics, and urinary 3-methylhistidine (3-MeH) excretion were examined in 12 men and women, aged 56–80 yr, before and during 12 wk of resistance training (R...
TL;DR: It is suggested that treatment with d-alpha-tocopherol can prevent diabetes-induced abnormalities in rat retinal blood flow and angiographic abnormalities of retinal hemodynamics based on computerized video-based fluorescein angiography and associated with increases of DAG and membranous PKC levels were also prevented.
Abstract: We have characterized effects of d-alpha-tocopherol (vitamin E) on activation of protein kinase C (PKC) and diacylglycerol (DAG) levels in retinal tissues of diabetic rats and correlated its effects to diabetes-induced changes in retinal hemodynamics. Membrane PKC specific activities were increased by 71% in streptozocin-induced diabetic rats compared with controls (P < 0.05). Western blot analysis showed that membrane PKC-beta II was increased by 133 +/- 5% (P < 0.05). Injection of d-alpha-tocopherol (40 mg/kg ip) every other day prevented the increases in membrane PKC specific activity and PKC-beta II protein by immunoblots. Diabetes-induced increases in DAG levels were also normalized by d-alpha-tocopherol treatment of 2 wk duration. Physiologically, angiographic abnormalities of retinal hemodynamics based on computerized video-based fluorescein angiography and associated with increases of DAG and membranous PKC levels were also prevented by d-alpha-tocopherol treatment in diabetic rats. The effect of d-alpha-tocopherol on retinal vascular cells was also studied. Exposure of retinal endothelial cells to 22 mM glucose for 3 days increased total DAG and [3H]palmitate-labeled DAG levels by 35 +/- 8 and 50 +/- 8% (P < 0.05), respectively, compared with exposure to 5.5 mM glucose. The presence of d-alpha-tocopherol (50 micrograms/ml) prevented the increases in total DAG and [3H]palmitate-labeled DAG levels in cells exposed to 22 mM glucose. These findings suggested that treatment with d-alpha-tocopherol can prevent diabetes-induced abnormalities in rat retinal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The data indicate that the decline in blood glucose during exercise in nonobese NIDDM is due to enhanced peripheral glucose utilization rather than to an attenuated increase in splanchnic glucose output.
Abstract: To characterize splanchnic and muscle metabolism during exercise in non-insulin-dependent diabetes mellitus (NIDDM), eight male nonobese patients and seven healthy control subjects (CON) were studi...
TL;DR: The impact of nutrition on muscle protein synthesis is blunted in old age, which could contribute to the age-related loss of nutrition-sensitive muscle proteins.
Abstract: This study was undertaken to determine whether the loss of muscle protein mass during aging could be explained by a reduced sensitivity of muscle protein synthesis to feeding and exercise. Male Wistar rats aged 12 and 24 mo were exercised by treadmill running for 4 mo. Protein synthesis was measured by the flooding dose method in tibialis anterior, soleus, and liver of conscious rested, trained rats and age-matched controls in the postprandial or in the postabsorptive state. No marked change with age could be detected in basal muscle protein synthesis. In contrast, protein synthesis was stimulated in adult but not in old rats by feeding in tibialis anterior and by exercise in soleus. In liver, protein synthesis was not modified by age but was stimulated by feeding and by exercise, which improved the response to feeding. We conclude that the impact of nutrition on muscle protein synthesis is blunted in old age, which could contribute to the age-related loss of nutrition-sensitive muscle proteins.
TL;DR: Impaired control at the level of the vascular system may have implications for long-term access of nutrients and hormones and therefore the control of skeletal muscle metabolism and contractile performance.
Abstract: Important differences exist between perfused and incubated (or perifused) skeletal muscle preparations with regard to their metabolism and control. A growing body of evidence suggests that the differences may be due to the role played by the vascular system. In the constant-flow perfused rat hindlimb preparation, a group of vasoconstrictors has been identified that enhance muscle metabolism and aerobic contractility. Another group of vasoconstrictors decrease muscle metabolism and aerobic contractility even though perfusate flow remains constant. All effects of both groups of vasoconstrictors are opposed by vasodilators. Because none of the vasoconstrictor effects is evident when isolated muscles are incubated or perifused, involvement of an active vascular system is indicated. Although some hormones may act directly on muscle by purely endocrine effects, a vascular component of their actions is now emerging. Mechanisms to account for vascular control of perfused skeletal muscle metabolism may involve 1) functional vascular shunts where the proportion of flow processed by these is regulated by site-specific vasomodulators, 2) a direct response to a change in the rate of supply of nutrients and removal of products, and 3) a signal substance released by vascular tissue in association with vasoconstriction that interacts with surrounding skeletal muscle cells. Impaired control at the level of the vascular system may have implications for long-term access of nutrients and hormones and therefore the control of skeletal muscle metabolism and contractile performance.
TL;DR: It is shown that acute hyperglycemia, similar to that observed in poorly controlled diabetic patients, produces relevant systemic hemodynamic changes and also alters baroreflex activity via a glutathione-sensitive presumably free radical-mediated pathway.
Abstract: The present study aimed at evaluating whether acute elevations of plasma glucose concentrations could influence systemic hemodynamic parameters and baroreflex activity in humans. Plasma glucose con...
TL;DR: Findings confirm previous studies in rodents demonstrating that DR alters glucose metabolism and may be related to the antiaging action of this intervention and also confirm several measures of the insulin response increased with age and were lower in DR monkeys.
Abstract: Male rhesus monkeys (Macaca mulatta) of different age groups representing the species life span were fed ad libitum or a 30% reduced calorie diet over a 7-yr period. During the first 2-3 yr of this longitudinal study, glucose and insulin levels were not altered by diet restriction (DR). However, reductions in fasting blood glucose became apparent in DR animals after 3-4 yr. At the end of the 6th yr of study, glycated hemoglobin was measured, and intravenous glucose tolerance tests (IVGTTs) were conducted. Maximum glucose levels reached during IVGTTs increased with age but were lower in DR animals compared with controls. Several measures of the insulin response (baseline, maximum, and integrated areas under curve) increased with age and were lower in DR monkeys. With the exception of glycated hemoglobin, which was not different in monkeys subjected to DR, these findings confirm previous studies in rodents demonstrating that DR alters glucose metabolism and may be related to the antiaging action of this intervention.
TL;DR: The results show that high-fat diets fed to adult animals cause increased body fat in the absence of significant changes in body weight and that mesenteric fat is increased disproportionately.
Abstract: This study examined the effects of increasing levels of dietary fat fed isocalorically on body weight, body composition, and adipose distribution. Adult male rats were weight matched into four groups. One group that was fed a low-fat diet (12%) served as reference controls. The other three groups were fed diets of 24, 36, or 48% fat in amounts to equal the energy intake of the control group. After 6 wk, body weights of the four groups were not significantly different. Intrascapular brown fat did not differ between groups. Total body fat and adipose depot weights, however, increased in proportion to the level of fat in the diet. Total body fat and retroperitoneal and mesenteric depot weights of the 48% fat group were greater than controls (P < 0.05). Mesenteric fat in this group was also significantly increased over all other groups (P < 0.05). These results show that high-fat diets fed to adult animals cause increased body fat in the absence of significant changes in body weight and that mesenteric fat is increased disproportionately.
TL;DR: It is concluded that a modest upregulation of glucose transport across the BBB takes place after starvation, which implies that the influx of ketone bodies into the brain is largely determined by the amount of ketones present in the blood, and any condition in which ketonemia occurs will lead to an increased ketone influx.
Abstract: The blood-brain barrier (BBB) permeability for glucose and beta-hydroxybutyrate (beta-OHB) was studied by the intravenous double-indicator method in nine healthy subjects before and after 3.5 days of starvation. In fasting, mean arterial plasma glucose decreased and arterial concentration of beta-OHB increased, whereas cerebral blood flow remained unchanged. The permeability-surface area product for BBB glucose transport from blood to brain (PS1) increased by 55 +/- 31%, whereas no significant change in the permeability from brain back to blood (PS2) was found. PS1 for beta-OHB remained constant during starvation. The expected increase in PS1 due to the lower plasma glucose concentration was calculated to be 22% using previous estimates of maximal transport velocity and Michaelis-Menten affinity constant for glucose transport. The determined increase was thus 33% higher than the expected increase and can only be partially explained by the decrease in plasma glucose. It is concluded that a modest upregulation of glucose transport across the BBB takes place after starvation. Brain transport of beta-OHB did not decrease as expected from the largely increased beta-OHB arterial level. This might be interpreted as an increase in brain transport of beta-OHB, which could be caused by induction mechanisms, but the large nonsaturable component of beta-OHB transport makes such a conclusion difficult. However, beta-OHB blood concentration and beta-OHB influx into the brain increased by > 10 times. This implies that the influx of ketone bodies into the brain is largely determined by the amount of ketones present in the blood, and any condition in which ketonemia occurs will lead to an increased ketone influx.
TL;DR: The regulation of the active form of pyruvate dehydrogenase and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise, indicating that muscle lactate production during exercise was not an O2-dependent process in the authors' subjects.
Abstract: The regulation of the active form of pyruvate dehydrogenase (PDHa) and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise. Seven subjects completed three consecutive 30-s bouts of maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the vastus lateralis were taken before and immediately after each bout. PDHa increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11, and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and 3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2 and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate production and oxidation resulted in substantial lactate accumulation to 89.5 +/- 11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in bout 3. These events coincided with an increase in the mitochondrial oxidation state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle lactate production during exercise was not an O2-dependent process in our subjects. During exercise the primary factor regulating PDHa transformation was probably intracellular Ca2+. In contrast, the primary regulatory factors causing greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased concentrations of pyruvate and H+. Greater PDHa during recovery facilitated continued oxidation of the lactate load between exercise bouts.