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Showing papers in "American Journal of Physiology-endocrinology and Metabolism in 1997"


Journal ArticleDOI
TL;DR: It is concluded that exercise resulted in an increase in muscle net protein balance that persisted for up to 48 h after the exercise bout and was unrelated to the type of muscle contraction performed.
Abstract: Mixed muscle protein fractional synthesis rate (FSR) and fractional breakdown rate (FBR) were examined after an isolated bout of either concentric or eccentric resistance exercise. Subjects were eight untrained volunteers (4 males, 4 females). Mixed muscle protein FSR and FBR were determined using primed constant infusions of [2H5]phenylalanine and 15N-phenylalanine, respectively. Subjects were studied in the fasted state on four occasions: at rest and 3, 24, and 48 h after a resistance exercise bout. Exercise was eight sets of eight concentric or eccentric repetitions at 80% of each subject's concentric 1 repetition maximum. There was no significant difference between contraction types for either FSR, FBR, or net balance (FSR minus FBR). Exercise resulted in significant increases above rest in muscle FSR at all times: 3 h = 112%, 24 h = 65%, 48 h = 34% (P < 0.01). Muscle FBR was also increased by exercise at 3 h (31%; P < 0.05) and 24 h (18%; P < 0.05) postexercise but returned to resting levels by 48 h. Muscle net balance was significantly increased after exercise at all time points [(in %/h) rest = -0.0573 +/- 0.003 (SE), 3 h = -0.0298 +/- 0.003, 24 h = -0.0413 +/- 0.004, and 48 h = -0.0440 +/- 0.005], and was significantly different from zero at all time points (P < 0.05). There was also a significant correlation between FSR and FBR (r = 0.88, P < 0.001). We conclude that exercise resulted in an increase in muscle net protein balance that persisted for up to 48 h after the exercise bout and was unrelated to the type of muscle contraction performed.

1,095 citations


Journal ArticleDOI
TL;DR: Evidence is provided that decreases in muscle content of malonyl-CoA can increase the rate of fatty acid oxidation, and perfusion with medium containing AICAR was found to activate AMPK in skeletal muscle, inactivate ACC, and decrease malony l-coA.
Abstract: 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5′-AMP This study was designed to determin

1,012 citations


Journal ArticleDOI
TL;DR: It is concluded that the stimulatory effect of exogenous amino acids on muscle protein synthesis is enhanced by prior exercise, perhaps in part because of enhanced blood flow, implying that protein intake immediately after exercise may be more anabolic than when ingested at some later time.
Abstract: Six normal untrained men were studied during the intravenous infusion of a balanced amino acid mixture (approximately 0.15 g.kg-1.h-1 for 3 h) at rest and after a leg resistance exercise routine to test the influence of exercise on the regulation of muscle protein kinetics by hyperaminoacidemia. Leg muscle protein kinetics and transport of selected amino acids (alanine, phenylalanine, leucine, and lysine) were isotopically determined using a model based on arteriovenous blood samples and muscle biopsy. The intravenous amino acid infusion resulted in comparable increases in arterial amino acid concentrations at rest and after exercise, whereas leg blood flow was 64 +/- 5% greater after exercise than at rest. During hyperaminoacidemia, the increases in amino acid transport above basal were 30-100% greater after exercise than at rest. Increases in muscle protein synthesis were also greater after exercise than at rest (291 +/- 42% vs. 141 +/- 45%). Muscle protein breakdown was not significantly affected by hyperminoacidemia either at rest or after exercise. We conclude that the stimulatory effect of exogenous amino acids on muscle protein synthesis is enhanced by prior exercise, perhaps in part because of enhanced blood flow. Our results imply that protein intake immediately after exercise may be more anabolic than when ingested at some later time.

823 citations


Journal ArticleDOI
TL;DR: The findings suggest a primarily inhibitory function for GLP-1 (ileal brake mechanisms) in normal subjects, and physiological doses still have a significant effect, despite the known insulinotropic actions of GLp-1-(7-36) amide and -(7-37).
Abstract: Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological an...

783 citations


Journal ArticleDOI
TL;DR: A decline in the synthesis rate of myosin heavy chain implies a decreased ability to remodel this important muscle contractile protein and likely contributes to the declining muscle mass and contractile function in the elderly.
Abstract: A decline in muscle mass and contractile function are prominent features of the sarcopenia of old age. Because myosin heavy chain is an important contractile protein, it was hypothesized that synth...

552 citations


Journal ArticleDOI
TL;DR: The ability of exercise to utilize insulin-independent mechanisms to increase glucose uptake in skeletal muscle has important clinical implications, especially for patients with diseases that are associated with peripheral insulin resistance, such as non-insulin-dependent diabetes mellitus.
Abstract: Exercise increases the rate of glucose uptake into the contracting skeletal muscles. This effect of exercise is similar to the action of insulin on glucose uptake, and the mechanism through which b...

398 citations


Journal ArticleDOI
TL;DR: Data demonstrate a leptin-induced increase in energy expenditure in nonmutant rodents and suggest that one mechanism by which leptin increases energy expenditure is through increased thermogenesis in BAT, including increased expression of UCP.
Abstract: In ob/ob mice, leptin increases energy expenditure and sympathetic outflow to brown adipose tissue (BAT). To test whether the mechanism of increased energy expenditure may involve increased thermogenesis in BAT, we acclimated normal rats to thermoneutrality for 2 wk followed by leptin administration for 1 wk. Some rats were food restricted for 1 wk to the level of food consumption in the leptin-treated ad libitum-fed rats, and the same rats were both food restricted and administered leptin for a second week. We examined oxygen consumption and uncoupling protein (UCP) expression in BAT. Leptin increased oxygen consumption after the 5th and 6th days in ad libitum-fed rats and after the 4th, 5th, and 6th days in food-restricted rats. Leptin increased BAT UCP mRNA levels greater than twofold in both ad libitum-fed and food-restricted rats. These data demonstrate a leptin-induced increase in energy expenditure in nonmutant rodents and suggest that one mechanism by which leptin increases energy expenditure is through increased thermogenesis in BAT, including increased expression of UCP.

398 citations


Journal ArticleDOI
TL;DR: It is concluded that an imbalance between TH1 and TH2 cells, decreased recruitment of T naive cells, and decreased percentage of T cytolytic cells may account for decreased cell-mediated immune functions in zinc-deficient subjects.
Abstract: We have utilized an experimental model of human zinc deficiency for study of cytokines production by TH1 and TH2 cells. Additionally, we determined ratios of CD4+ to CD8+ and CD4+ CD45RA+ to CD4+CD...

326 citations


Journal ArticleDOI
TL;DR: It is suggested that GLP-2 regulates both cell proliferation and apoptosis and promotes intestinal growth after both short- and long-term administration in vivo.
Abstract: Glucagon-like peptide-2 (GLP-2) has been shown to promote intestinal epithelial proliferation. We studied crypt cell proliferation, enterocyte cell death, and feeding behavior in GLP-2-treated mice. GLP-2 had no effect on food consumption [7.7 +/- 0.3 vs. 8.0 +/- 0.4 g/day, saline (control) vs. GLP-2-treated mice, P = not significant]; however, GLP-2 increased the crypt cell proliferation rate (46.0 +/- 1 vs. 57 +/- 5%, control vs. GLP-2, P < 0.01) and decreased the enterocyte apoptotic rate (5.9 +/- 0.7 vs. 2.8 +/- 0.2% apoptotic cells, control vs. GLP-2, P < 0.05) in small bowel (SB) epithelium. GLP-2 induced a significant increase in SB weight (1.3- to 1.75-fold increase over control, P < 0.05 to P < 0.001) in mice 1-24 mo of age. Increased SB weight was maintained after daily administration of GLP-2 to mice for 12 wk, and cessation of GLP-2 administration in older mice led to regression of (increased) SB weight and mucosal height. These observations suggest that GLP-2 regulates both cell proliferation and apoptosis and promotes intestinal growth after both short- and long-term administration in vivo.

307 citations


Journal ArticleDOI
TL;DR: Dietary fat intake acts as a background form of chronic stress, elevating basal B levels and enhancing HPA responses to stress, suggesting support for the specificity of the effects on the HPA axis.
Abstract: High-fat feeding induces insulin resistance and increases the risk for the development of diabetes and coronary artery disease. Glucocorticoids exacerbate this hyperinsulinemic state, rendering an ...

301 citations


Journal ArticleDOI
TL;DR: Sub substrate oxidation during exercise can be regulated by increased glycolytic flux that is accompanied by a direct inhibition of long-chain fatty acid oxidation, as indicated by a coordination of effects on adipose tissue and muscle.
Abstract: We determined whether increased glycolytic flux from hyperglycemia and hyperinsulinemia directly reduces fatty acid oxidation during exercise. Fatty acid oxidation rates were measured during constant-rate intravenous infusion of trace amounts of a long-chain fatty acid ([1-13C]palmitate; Pal) vs. a medium-chain fatty acid ([1-13C]octanoate; Oct). Six endurance-trained men cycled for 40 min at 50% of maximal O2 uptake 1) after an overnight fast (“fasting”) and 2) after ingestion of 1.4 g/kg of glucose at 60 min and again 10 min before exercise (Glc). Glc caused hyperinsulinemia, a preexercise blood glucose of 6 mM, and a 34% reduction in total fat oxidation during exercise due to an approximately equal reduction in oxidation of plasma-free fatty acids (FFA) and intramuscular triglycerides (all P < 0.05). Oxidation of Pal was significantly reduced during Glc compared with fast (i.e., 70.0 +/- 4.1 vs. 86.0 +/- 1.9% of tracer infusion rate; P < 0.05). However, Glc had no effect on Oct oxidation, which is apparently not limited by mitochondrial transport. Furthermore, Glc reduced plasma FFA appearance 36% (P < 0.05), indicating a coordination of effects on adipose tissue and muscle. In summary, substrate oxidation during exercise can be regulated by increased glycolytic flux that is accompanied by a direct inhibition of long-chain fatty acid oxidation. These observations indicate that carbohydrate availability can directly regulate fat oxidation during exercise.

Journal ArticleDOI
TL;DR: The results suggest that MCT1 may play an important role in the passage of lactate and other monocarboxylates across the blood-brain barrier and that suckling rats may be especially dependent on this transporter to supply energy substrates to the brain.
Abstract: A polyclonal affinity-purified antibody to the carboxyl-terminal end of the rat monocarboxylate transporter 1 (MCT1) was generated in chickens and used in immunocytochemical studies of brain tissue sections from adult and suckling rats. The antibody identified a 48-kDa band on immunoblots and stained tissue sections of heart, cecum, kidney, and skeletal muscle, consistent with the reported molecular mass and cellular expression for this transporter. In tissue sections from adult brains, the antibody labeled brain microvessel endothelial cells, ependymocytes, glial-limiting membranes, and neuropil. In brain sections from 3- to 14-day-old rats, microvessels were much more strongly labeled and neuropil was weakly labeled compared with sections from adults. Immunoelectron microscopy indicated that labeling was present on both luminal and abluminal endothelial cell plasma membranes. These results suggest that MCT1 may play an important role in the passage of lactate and other monocarboxylates across the blood-brain barrier and that suckling rats may be especially dependent on this transporter to supply energy substrates to the brain.

Journal ArticleDOI
TL;DR: Small elevations in plasma insulin before exercise suppressed lipolysis during exercise to the point at which it equaled and appeared to limit fat oxidation.
Abstract: This study determined if the suppression of lipolysis after preexercise carbohydrate ingestion reduces fat oxidation during exercise. Six healthy, active men cycled 60 min at 44 +/- 2% peak oxygen consumption, exactly 1 h after ingesting 0.8 g/kg of glucose (Glc) or fructose (Fru) or after an overnight fast (Fast). The mean plasma insulin concentration during the 50 min before exercise was different among Fast, Fru, and Glc (8 +/- 1, 17 +/- 1, and 38 +/- 5 microU/ml, respectively; P < 0.05). After 25 min of exercise, whole body lipolysis was 6.9 +/- 0.2, 4.3 +/- 0.3, and 3.2 +/- 0.5 micromol x kg(-1) x min(-1) and fat oxidation was 6.1 +/- 0.2, 4.2 +/- 0.5, and 3.1 +/- 0.3 micromol x kg(-1) x min(-1) during Fast, Fru, and Glc, respectively (all P < 0.05). During Fast, fat oxidation was less than lipolysis (P < 0.05), whereas fat oxidation approximately equaled lipolysis during Fru and Glc. In an additional trial, the same subjects ingested glucose (0.8 g/kg) 1 h before exercise and lipolysis was simultaneously increased by infusing Intralipid and heparin throughout the resting and exercise periods (Glc+Lipid). This elevation of lipolysis during Glc+Lipid increased fat oxidation 30% above Glc (4.0 +/- 0.4 vs. 3.1 +/- 0.3 micromol x kg(-1) x min(-1); P < 0.05), confirming that lipolysis limited fat oxidation. In summary, small elevations in plasma insulin before exercise suppressed lipolysis during exercise to the point at which it equaled and appeared to limit fat oxidation.

Journal ArticleDOI
TL;DR: In this paper, obesity is associated with both insulin resistance and hyperinsulinemia, which is a condition that compensates for the insulin resistance by maintaining normal glucose homeostasis.
Abstract: Obesity is associated with both insulin resistance and hyperinsulinemia. Initially hyperinsulinemia compensates for the insulin resistance and thereby maintains normal glucose homeostasis. Obesity ...

Journal ArticleDOI
TL;DR: Induction of intestinal growth by GLP-2 in wild-type mice results in a normal-to-increased capacity for nutrient digestion and absorption in vivo.
Abstract: Glucagon-like peptide-2 (GLP-2) stimulates small intestinal growth through induction of intestinal epithelial proliferation. To examine the physiology of GLP-2-induced bowel, mice were treated with GLP-2 (2.5 micrograms) or vehicle for 10 days. Small intestinal weight increased to 136 +/- 2% of controls in GLP-2-treated mice, in parallel with 1.4 +/- 0.1- and 1.9 +/- 0.5-fold increments in duodenal RNA and protein content, respectively (P < 0.05-0.001). Similarly, the activities of duodenal maltase, sucrase, lactase, glutamyl transpeptidase, and dipeptidyl-peptidase IV (215 +/- 28% of controls; P < 0.001) were increased by GLP-2. Oral or duodenal administration of glucose or maltose did not reveal any differences in the ability of GLP-2-treated mice to absorb these nutrients, possibly because of decreases in expression of the glucose transporters sodium-dependent glucose transporter-1 (SGLT-1) and GLUT-2. In contrast, absorption of leucine plus triolein was increased after duodenal administration in GLP-2-treated mice (P < 0.01-0.001). Finally, GLP-2 did not alter other markers of intestinal or pancreatic gene expression, including levels of mRNA transcripts for ornithine decarboxylase, multidrug resistance gene, amylase, proglucagon, proinsulin, and prosomatostatin. Thus induction of intestinal growth by GLP-2 in wild-type mice results in a normal-to-increased capacity for nutrient digestion and absorption in vivo.

Journal ArticleDOI
TL;DR: Exercise-induced changes in functional properties of ACC appear to be contraction mediated and are accompanied by increased AMPK activity and an increase in the estimated free AMP.
Abstract: Muscle malonyl-CoA decreases during exercise or electrical stimulation, the exercise-induced decline being accompanied by changes in the kinetic properties [maximal velocity (Vmax), activation cons

Journal ArticleDOI
TL;DR: The data suggest that mechanical loading of bone is sensed by osteoblastic cells through fluid flow-mediated wall-shear stress rather than by mechanical strain.
Abstract: The nature of the stimulus sensed by bone cells during mechanical usage has not yet been determined. Because nitric oxide (NO) and prostaglandin (PG) production appear to be essential early respons...

Journal ArticleDOI
TL;DR: Product of NO synthase, NO and citrulline, were shown to inhibit MPEC arginase activity under maximal assay conditions, and this reciprocal change in arginine metabolism is proposed to be an important component of wound healing.
Abstract: Nitric oxide (NO) and ornithine, products of NO synthase or arginase, respectively, have opposing biological activities. The effect of mediators of leukocyte activation and inhibition on arginine metabolism of resident mouse peritoneal exudate cells (MPEC) was determined. Factors that increased basal NO synthase activity, interferon (IFN)-gamma and lipopolysaccharide (LPS), decreased arginase activity in intact cells. Transforming growth factor (TGF)-beta1 decreased IFN-gamma-stimulated NO synthase activity and produced a reciprocal increase in urea and ornithine release. TGF-beta1 had no effect on the activity of these enzymes in LPS-stimulated MPEC. Corticosterone (Cort, 100 ng/ml) decreased the basal activity of both enzymes. However, Cort inhibited NO synthase activity and increased ornithine release in MPEC exposed to IFN-gamma or LPS. The difference between arginase activity in intact cells vs. that of cell lysates suggested intracellular inhibition of arginase activity. Products of NO synthase, NO and citrulline, were shown to inhibit MPEC arginase activity under maximal assay conditions. Intracellular pH was not altered by exposure of MPEC to LPS, IFN-gamma, TGF-beta, and Cort. This reciprocal change in arginine metabolism is proposed to be an important component of wound healing. Expression of NO synthase creates a cytotoxic environment that may be important to the early phase of wound healing. As wound healing progresses, increased arginase activity produces an environment favorable for fibroblast replication and collagen production.

Journal ArticleDOI
TL;DR: The data suggest that oxidant stress alters glucose transporters expression and insulin-stimulated metabolism in 3T3-L1 adipocytes, resulting in a right shift in the insulin dose-response curve.
Abstract: Increased oxidant stress has been suggested to occur in diabetes and to contribute to the development of late diabetic complications. Whether oxidant stress plays a role in the development or progr...

Journal ArticleDOI
TL;DR: It is concluded that nitric oxide is involved in the signal transduction mechanism to increase glucose transport during exercise, and there are separate pathways for contraction- and insulin-stimulated glucose transport.
Abstract: It has been suggested that there are separate insulin-stimulated and contraction-stimulated glucose transport pathways in skeletal muscle. This study examined the effects of nitric oxide on glucose transport in rat skeletal muscle by use of an isolated sarcolemmal membrane preparation and the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), administered in the drinking water (1 mg/ml). Female Sprague-Dawley rats were divided into five groups: control, acute exercise, acute exercise+L-NAME, insulin stimulated, and insulin stimulated+L-NAME. Exercise (45 min of exhaustive treadmill running) increased glucose transport (37 +/- 2 to 76 +/- 5 pmol.mg-1.15 s-1) and this increase was completely inhibited by L-NAME (40 +/- 4 pmol.mg-1.15 s-1). A maximum dose of insulin increased glucose transport (87 +/- 10 pmol.mg-1.15 s-1), and adding L-NAME had no effect (87 +/- 11 pmol.mg-1.15 s-1). In addition, exercise, but not exercise+L-NAME, increased sarcolemma GLUT-4 content. This study confirms that there are separate pathways for contraction- and insulin-stimulated glucose transport. More importantly, although exercise and insulin both significantly increased glucose transport, L-NAME had no effect on insulin-stimulated glucose transport but blocked the exercise-stimulated transport. We conclude that nitric oxide is involved in the signal transduction mechanism to increase glucose transport during exercise.

Journal ArticleDOI
TL;DR: The loss of (14)C label from TG in SOL during the chase without palmitate was not accompanied by a significant change in TG content, suggesting that, during rest, there is a small subpool of TG with a relatively rapid turnover.
Abstract: Intramuscular lipid pool turnover [triacylglycerols (TG), phospholipids (PL), mono- and diacylglycerols (MG, DG)] and the oxidation of endogenous and exogenous lipids were determined with pulse-chase studies in incubated muscles of varied oxidative potential [soleus strips (SOL)--> epitrochlearis --> flexor digitorum brevis]. Incorporation of palmitate into TG and PL pools and its oxidation were linearly related to time and exogenous palmitate concentration in all muscles. Total palmitate incorporation (deposition and oxidation) was greatest in SOL. However, palmitate incorporation into TG was similar in all muscles when expressed as a percentage of the total incorporation. In contrast, palmitate incorporation into PL was greatest in the least oxidative muscle. Palmitate oxidation, incorporation into TG, and citrate synthase activity were all strongly correlated with muscle cytosolic fatty acid-binding protein content (r = 0.96, 1.0, and 0.98, respectively). During the chase, reducing exogenous palmitate from 1.0 mM to 0.5 or 0 mM resulted in a significant (approximately 30%) loss of [(14)C]palmitate from the TG pool in SOL and a significant increase in (14)CO(2) production from endogenous stores. No significant loss of (14)C label from lipid pools occurred in the less oxidative muscles, suggesting a closely regulated interaction between energy provision from exogenous and endogenous lipid pools in oxidative muscle. Glucose oxidation increased significantly in all muscles in the absence of palmitate. The loss of (14)C label from TG in SOL during the chase without palmitate was not accompanied by a significant change in TG content. This suggests that, during rest, there is a small subpool of TG with a relatively rapid turnover.

Journal ArticleDOI
TL;DR: The time course of the LPL response to both short-term and acute exercise was examined and circulating levels of putative regulators of muscle LPL were measured to suggest induction of LPL gene expression may result from dynamic changes in serum catecholamines, plasma insulin, or events intrinsic to muscle contraction itself.
Abstract: Exercise increases skeletal muscle lipoprotein lipase (LPL) expression, but the time course of this response is not known. In the present study, we examined the time course of the LPL response to both short-term and acute exercise and measured circulating levels of putative regulators of muscle LPL. Nine adults underwent short-term exercise training (60-90 min of stationary cycling at 55-70% of leg ergometer peak oxygen uptake on 5 consecutive days). Five vastus lateralis biopsies were performed: before training, 20 h after the fourth bout (immediately before the 5th bout), and 0.2, 4, and 8 h after the fifth bout. After four bouts of exercise in 4 days, there was no increase in LPL mass or LPL mRNA exactly 20 h after the fourth bout. However, when tissues were sampled closer to the exercise bout on the 5th day, transient increases were seen. On day 5, LPL mRNA increased by 127% (P < 0.05) at 4 h postexercise and was followed by an increase in LPL mass of 93% (P < 0.05) at 8 h postexercise. Serum triglycerides decreased by 23% (P < 0.05) during the protocol. Two nonexercising subjects showed no consistent change in LPL mRNA or mass. Acute exercise transiently increased levels of norepinephrine (9-fold) and epinephrine (5-fold) and reduced insulin levels. Acute exercise preceded by four daily bouts of exercise induces a transient rise in LPL mRNA followed by rise in LPL mass, suggesting that these responses are temporally related. This induction of LPL gene expression may result from dynamic changes in serum catecholamines, plasma insulin, or events intrinsic to muscle contraction itself.

Journal ArticleDOI
TL;DR: The data suggest that 1) women have higher circulating leptin concentrations despite lower fat mass and 2) exercise training appears to have a greater effect on systemic leptin levels in females than in males.
Abstract: Leptin, the product of the ob gene, is elevated in obese humans and appears to be closely related to body fat content. The purpose of the present investigation was to determine the effect of aerobi...

Journal ArticleDOI
TL;DR: It is concluded that abdominal fat is the major determinant of GH secretion in healthy nonobese adults, and the clinical implications of visceral adiposity to include hyposomatotropism are extended.
Abstract: We tested the hypothesis that body composition is the major predictor of growth hormone (GH) secretion in nonobese adults. We measured lean and fat tissue distribution (computerized tomography and dual-energy X-ray absorptiometry scan) and physical fitness [maximal oxygen consumption (Vo2max)] in 42 healthy nonobese adults (22 women and 20 men, age range 27-59 yr, mean +/- SE body mass index = 24 +/- 0.5 kg/m2). Deconvolution analysis was used to estimate specific features of 24-h GH secretion and clearance. Approximate entropy was used to quantify the regularity of GH release. Older subjects exhibited decreased estimates of GH secretion compared with younger subjects. Females had higher estimates of GH secretion, a longer GH half-life, and displayed more irregularity in GH release than males. Mean 24-h serum GH concentrations correlated inversely with intra-abdominal fat and waist-to-hip ratio and positively with Vo2max. Multiple linear regression analysis revealed intra-abdominal fat as the dominant determinant of estimates of GH secretion. Vo2max was more important than sex and age in predicting GH secretion. We conclude that abdominal fat is the major determinant of GH secretion in healthy nonobese adults. Although the underlying mechanisms remain elusive, our findings extend the clinical implications of visceral adiposity to include hyposomatotropism.

Journal ArticleDOI
TL;DR: It is indicated that nocturnal physical activity may phase delay human circadian rhythms and demonstrates that phase-shifting effects may be determined with exercise durations and intensities compatible with the demands of a real-life setting.
Abstract: To determine the roles of intensity and duration of nocturnal physical activity in causing rapid phase shifts of human circadian rhythms, eight healthy men were studied three times under constant c...

Journal ArticleDOI
TL;DR: It is concluded that, in fed piglets, mucosal GSH-glutamate derived largely from the direct metabolism of enteral glutamate rather than from glutamate that was metabolized within the mucosa.
Abstract: To measure the source and rate of mucosal glutathione (GSH) synthesis, fed piglets (28 days old; 7.7 kg) received a 6-h infusion of intragastric [U-13C]glutamate (n = 11) either with (n = 5) or without (n = 6) an intragastric infusion of [1-13C]glycine (0-6 h) and [1,2-13C2(U-13C)]glycine (3-6 h). Eighty-four percent of the labeled mucosal GSH-glutamate and 86% of the luminal GSH-glutamate was 13C5. The tracer-to-tracee ratio of GSH-[U-13C]glutamate was 75% of that of mucosal glutamate. Sixty percent of the labeled mucosal glutamate was 13C1, 13C2, or 13C3, but the tracer-to-tracee ratios of these isotopomers in GSH-glutamate were not significantly different from zero. After 3 h of infusion, the tracer-to-tracee ratio of GSH-[U-13C]glycine was 46%, and after 6 h of infusion GSH-[13C1]glycine was 82% of that of mucosal glycine. This suggested that the half-life of mucosal GSH was 2.7 +/- 0.1 h. We concluded that, in fed piglets, mucosal GSH-glutamate derived largely from the direct metabolism of enteral glutamate rather than from glutamate that was metabolized within the mucosa.

Journal ArticleDOI
TL;DR: Some of the observed changes in sleep architecture and sleep-EEG power spectra are similar to those induced by agonistic modulators of the GABAA receptor complex and appear to be mediated in part via the conversion of progesterone into its GABA-active metabolites.
Abstract: Progesterone administration induces a reduction of the vigilance state in humans during wakefulness. It has been been suggested that this effect is mediated via neuroactive metabolites that interact with the gamma-aminobutyric, acidA (GABAA) receptor complex. To investigate the effects of progesterone administration on the sleep electroencephalogram (EEG) in humans we made polysomnographic recordings, including sleep stage-specific spectral analysis, and concomitantly measured plasma concentrations of progesterone and its GABA-active metabolites 3 alpha-hydroxy-5 alpha-dihydroprogesterone (allopregnanolone) and 3 alpha-hydroxy-5 beta-dihydroprogesterone (pregnanolone) in nine healthy male subjects in a double-blind placebo-controlled crossover study. Progesterone administration at 9:30 PM induced a significant increase in the amount of non-rapid eye movement (REM) sleep. The EEG spectral power during non-REM sleep showed a significant decrease in the slow wave frequency range (0.4-4.3 Hz), whereas the spectral power in the higher frequency range (> 15 Hz) tended to be elevated. Some of the observed changes in sleep architecture and sleep-EEG power spectra are similar to those induced by agonistic modulators of the GABAA receptor complex and appear to be mediated in part via the conversion of progesterone into its GABA-active metabolites.

Journal ArticleDOI
TL;DR: The data suggest that, in addition to suboptimal FFA availability, fatty acid oxidation is likely limited during high-intensity exercise because of direct inhibition of long-chain fatty acid entry into mitochondria.
Abstract: In the present study we examined the hypothesis that fatty acid oxidation is less during high-intensity exercise than during moderate-intensity exercise because of inhibition of long-chain fatty acid entry into the mitochondria. Six volunteers exercised at 40% peak oxygen consumption (VO2peak) for 60 min and at 80% VO2peak for 30 min on two different occasions. [1-13C]oleate, a long-chain fatty acid, and [1-14C]octanoate, a medium-chain fatty acid, were infused for the duration of the studies. Lipids and heparin were infused during exercise at 80% VO2peak to prevent the expected decrease in plasma free fatty acid (FFA) concentration. Plasma oleate and total FFA availability were similar in the two experiments. Oleate oxidation decreased from 2.8 +/- 0.6 (40% VO2peak) to 1.8 +/- 0.2 mumol.kg-1.min-1 (80% VO2peak, P < 0.05), whereas octanoate oxidation increased from 1.0e-05 +/- 1.0e-06 (40% VO2peak) to 1.3e-05 +/- 5.1e-06 mumol.kg-1.min-1 (80% VO2peak, P < 0.05). Furthermore, the percentage of oleate uptake oxidized decreased from 67.7 +/- 2.8% (40% VO2peak) to 51.8 +/- 4.6% (80% VO2peak, P < 0.05), whereas the percentage of octanoate oxidized was similar during exercise at 40 and 80% VO2peak (84.8 +/- 2.7 vs. 89.3 +/- 2.7%, respectively). Our data suggest that, in addition to suboptimal FFA availability, fatty acid oxidation is likely limited during high-intensity exercise because of direct inhibition of long-chain fatty acid entry into mitochondria.

Journal ArticleDOI
TL;DR: The results suggest that poor fetal nutrition during pregnancy and lactation can have long-term effects on glucose transport and on the expression of key components of the insulin signaling pathway in adipocytes.
Abstract: Insulin action on adipocytes was studied in the offspring of mothers who had been fed either a control (20% protein) or a low (8%)-protein diet during pregnancy and lactation. Adipocytes isolated from low-protein offspring had significantly higher basal and insulin-stimulated glucose uptakes than controls. This may be related to a threefold increase in insulin receptors in low-protein adipocytes. Consistent with these observed changes in glucose transport, adipocytes from low-protein animals had significantly higher basal and insulin-stimulated insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activities. There was also more p85-associated PI 3-kinase activity in these adipocytes. There was no difference in expression in the p85 regulatory subunit or the p110-alpha catalytic subunit of PI 3-kinase. In contrast, there was a sixfold reduction in the p110-beta catalytic subunit of PI 3-kinase in adipocytes from low-protein animals. These results suggest that poor fetal nutrition during pregnancy and lactation can have long-term effects on glucose transport and on the expression of key components of the insulin signaling pathway in adipocytes.

Journal ArticleDOI
TL;DR: %GNG increases gradually from the postabsorptive state to 42 h of fasting, without apparent change in the quantity of glucose produced by gluconeogenesis at 14 and 22 h, as determined from hydrogen enrichments at blood glucose C-2, C-5, and C-6.
Abstract: The use of2H2O in estimating gluconeogenesis’ contribution to glucose production (%GNG) was examined during progressive fasting in three groups of healthy subjects. One group (n = 3) ingested2H2O t...