bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy expenditure in children predicted from heart rate and activity calibrated against respiration calorimetry
Authors: Treuth Margarita S. , Adolph Anne L. , Butte Nancy F.
Published: December 2017

The purpose of this study was to predict energy expenditure (EE) from heart rate (HR) and activity calibrated against 24-h respiration calorimetry in 20 children. HR, oxygen consumption (V˙o 2), carbon dioxide production (V˙co 2), and EE were measured during rest, sleep, exercise, and over 24 h by room respiration calorimetry on two separate occasions. Activity was monitored by a leg vibration sensor. The calibration day ( day 1) consisted of specified behaviors categorized as inactive (lying, sitting, standing) or active (two bicycle sessions). On the validation day ( day 2), the child selected activities. Separate regression equations forV˙o 2,V˙co 2, and EE for method 1 (combining awake and asleep using HR, HR2, and HR3), method 2 (separating awake and asleep), and method 3 (separating awake into active and inactive, and combining activity and HR) were developed using the calibration data. For day 1, the errors were similar for 24-hV˙o 2,V˙co 2, and EE among methods and also among HR, HR2, and HR3. The methods were validated using measured data from day 2. There were no significant differences in HR,V˙o 2,V˙co 2, respiratory quotient, and EE values during rest, sleep, or over the 24 h between days 1 and 2. Applying the linear HR equations to day 2 data, the errors were the lowest with the combined HR/activity method (−2.6 ± 5.2%, −4.1 ± 5.9%, −2.9 ± 5.1% forV˙o 2,V˙co 2, and EE, respectively). To demonstrate the utility of the HR/activity method, HR and activity were monitored for 24 h at home ( day 3). Free-living EE was predicted as 7,410 ± 1,326 kJ/day. In conclusion, the combination of HR and activity is an acceptable method for determining EE not only for groups of children, but for individuals.
Perioperative insulin and glucose infusion maintains normal insulin sensitivity after surgery
Authors: Nygren Jonas O. , Thorell Anders , Soop Mattias , Efendic Suad , Brismar Kerstin , Karpe Fredrik , Nair K. S. , Ljungqvist Olle
Published: December 2017

Elective surgery was performed after overnight fasting, a routine that may affect the metabolic response to surgery. We investigated the effects of insulin and glucose infusions before and during surgery on postoperative substrate utilization and insulin sensitivity. Seven patients were given insulin and glucose infusions 3 h before and during surgery (insulin group), and a control group of six patients underwent surgery after fasting overnight. Insulin sensitivity and glucose kinetics (d-[6,6-2H2]glucose) were measured before and immediately after surgery using a hyperinsulinemic, normoglycemic clamp. Glucose infusion rates and whole body glucose disposal decreased after surgery in the control group (−40 and −29%, respectively), whereas no significant change was found in the insulin group (+16 and +25%). Endogenous glucose production remained unchanged in both groups. Postoperative changes in cortisol, glucagon, fat oxidation, and free fatty acids were attenuated in the insulin group (vs. control). We conclude that perioperative insulin and glucose infusions minimize the endocrine stress response and normalize postoperative insulin sensitivity and substrate utilization.
Insulin-dependent protein trafficking in skeletal muscle cells
Authors: Zhou Min , Sevilla Lidia , Vallega Gino , Chen Peng , Palacin Manuel , Zorzano Antonio , Pilch Paul F. , Kandror Konstantin V.
Published: December 2017

We have established a simple procedure for the separation of intracellular pool(s) of glucose transporter isoform GLUT-4-containing vesicles from the surface sarcolemma and T tubule membranes of rat skeletal myocytes. This procedure enabled us to immunopurify intracellular GLUT-4-containing vesicles and to demonstrate that 20–30% of the receptors for insulin-like growth factor II/mannose 6-phosphate and transferrin are colocalized with GLUT-4 in the same vesicles. Using our new fractionation procedure as well as cell surface biotinylation, we have shown that these receptors are translocated from their intracellular compartment(s) to the cell surface along with GLUT-4 after insulin stimulation in vivo. Denervation causes a considerable downregulation of GLUT-4 protein in skeletal muscle but does not affect the level of expression of other known component proteins of the corresponding vesicles. Moreover, the sedimentation coefficient of these vesicles remains unchanged by denervation. We suggest that the normal level of GLUT-4 expression is not necessary for the structural organization and insulin-sensitive translocation of its cognate intracellular compartment.
Utilization of skeletal muscle triacylglycerol during postexercise recovery in humans
Authors: Kiens Bente , Richter Erik A.
Published: December 2017

The utilization of muscle triacylglycerols was studied during and after prolonged bicycle ergometer exercise to exhaustion in eight healthy young men. Two days before exercise and in the postexercise recovery period, subjects were fed a carbohydrate-rich diet (65–70% of energy from carbohydrates). Exercise decreased muscle glycogen concentrations from 533 ± 18 to 108 ± 10 mmol/kg dry wt, whereas muscle triacylglycerol concentrations were unaffected (49 ± 5 before vs. 49 ± 8 mmol/kg dry wt after exercise). During the first 18 h after exercise, muscle glycogen concentrations were restored to 409 ± 20 mmol/kg dry wt. In contrast, muscle triacylglycerol concentrations decreased ( P < 0.05) to a nadir of 38 ± 5 mmol/kg dry wt, and muscle lipoprotein lipase activity increased by 72% compared with values before exercise. Pulmonary respiratory exchange ratio values of 0.80–0.82 indicated a relatively high fractional lipid combustion despite the high carbohydrate intake. From 18 to 42 h of recovery, muscle glycogen synthesis was slow and muscle triacylglycerol concentrations and lipoprotein lipase activity were restored to the preexercise values. It is concluded that muscle triacylglycerol concentrations are not diminished during exhaustive glycogen-depleting exercise. However, in the postexercise recovery period, muscle glycogen resynthesis has high metabolic priority, resulting in postexercise lipid combustion despite a high carbohydrate intake. It is suggested that muscle triacylglycerols, and probably very low density lipoprotein triacylglycerols, are important in providing fuel for muscle metabolism in the postexercise recovery period.
Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy
Authors: Criswell David S. , Booth Frank W. , DeMayo Franco , Schwartz Robert J. , Gordon Scott E. , Fiorotto Marta L.
Published: December 2017

This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups ( n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced ( P < 0.05) after HU in both IGF-I (−9%) and FVB mice (−13%). Contrary to our hypothesis, we found that the relative abundance of mRNA for the endogenous rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced ( P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.
Whole body fat oxidation is related to in situ adipose tissue lipolytic response to isoproterenol in males
Authors: Snitker S. , Hellmér J. , Boschmann M. , Monroe M. B. , Ravussin E.
Published: December 2017

A high 24-h respiratory quotient (RQ), i.e., low fat oxidation, predicts weight gain. To determine whether impaired fat mobilization (lipolysis) may contribute to weight gain, we studied the relation between lipolytic response to nonselective β-adrenergic stimulation and RQ measured in a respiratory chamber in 21 males (11 Caucasians, 10 Pima Indians; age 32 ± 5 yr, weight 93 ± 24 kg, body fat 30 ± 8%; means ± SD) and 23 females (10 Caucasians, 13 Pima Indians; age 32 ± 9 yr, weight 95 ± 26 kg, body fat 44 ± 8%). Lipolytic response was assessed as the relative increase in dialysate glycerol concentration (% above baseline) when isoproterenol (1 μmol/l) was added to the perfusate of a microdialysis probe inserted in the abdominal subcutaneous adipose tissue. In males, but not in females, basal RQ measured during sleep from 0500 to 0630 and adjusted for waist circumference was negatively correlated to lipolytic response ( r = −0.66, P = 0.001). The results suggest that in males, impaired β-adrenergic-mediated lipolysis may contribute to low rates of fat oxidation, a condition known to predispose to weight gain.
Mutational analysis of the carboxy-terminal phosphorylation site of GLUT-4 in 3T3-L1 adipocytes
Authors: Marsh Brad J. , Martin Sally , Melvin Derek R. , Martin Laura B. , Alm Richard A. , Gould Gwyn W. , James David E.
Published: December 2017

The carboxy terminus of GLUT-4 contains a functional internalization motif (Leu-489Leu-490) that helps maintain its intracellular distribution in basal adipocytes. This motif is flanked by the major phosphorylation site in this protein (Ser-488), which may play a role in regulating GLUT-4 trafficking in adipocytes. In the present study, the targeting of GLUT-4 in which Ser-488 has been mutated to alanine (SAG) has been examined in stably transfected 3T3-L1 adipocytes. The trafficking of SAG was not significantly different from that of GLUT-4 in several respects. First, in the absence of insulin, the distribution of SAG was similar to GLUT-4 in that it was largely excluded from the cell surface and was enriched in small intracellular vesicles. Second, SAG exhibited insulin-dependent movement to the plasma membrane (4- to 5-fold) comparable to GLUT-4 (4- to 5-fold). Finally, okadaic acid, which has previously been shown to stimulate both GLUT-4 translocation and its phosphorylation at Ser-488, also stimulated the movement of SAG to the cell surface similarly to GLUT-4. Using immunoelectron microscopy, we have shown that GLUT-4 is localized to intracellular vesicles containing the Golgi-derived γ-adaptin subunit of AP-1 and that this localization is enhanced when Ser-488 is mutated to alanine. We conclude that the carboxy-terminal phosphorylation site in GLUT-4 (Ser-488) may play a role in intracellular sorting at the trans-Golgi network but does not play a major role in the regulated movement of GLUT-4 to the plasma membrane in 3T3-L1 adipocytes.
The opiate sufentanil alters the inflammatory, endocrine, and metabolic responses to endotoxin in dogs
Authors: Moeniralam Hazra S. , Endert Erik , Ackermans Mariëtte T. , Van Lanschot J. Jan B. , Sauerwein Hans P. , Romijn Johannes A.
Published: December 2017

Sufentanil is a synthetic μ-opioid receptor agonist frequently used in anesthesia and critically ill patients. To evaluate the effects of sufentanil on the inflammatory, neuroendocrine, and metabolic responses to endotoxin, we studied six dogs during saline infusion (control), during sufentanil infusion (1.5 μg ⋅ kg−1⋅ h−1), after endotoxin injection (1.0 μg/kg iv), and during combined endotoxin and sufentanil administration. The rate of appearance of glucose was determined by infusion of [6,6-2H2]glucose. Sufentanil depressed the endotoxin-induced increase in body temperature (36.9 ± 0.3 vs. 40.6 ± 0.5°C, P < 0.05). Sufentanil depressed the tumor necrosis factor (TNF) response to endotoxin by ∼60% ( P < 0.01) but increased the interleukin-6 (IL-6) response by ∼70% ( P < 0.01). Sufentanil per se induced a transient neuroendocrine activation. Sufentanil also increased plasma concentrations of insulin and catecholamines after endotoxin ( P < 0.05 vs. endotoxin alone) and increased plasma glucose levels by ∼36% (from 6.1 ± 0.1 to 8.3 ± 0.6 mmol/l, P < 0.05 vs. endotoxin alone). Endotoxin stimulated glucose production transiently by 95% (24.2 ± 3.2 vs. control 12.4 ± 1.0 μmol ⋅ kg−1⋅ min−1, P < 0.05). Paradoxically, sufentanil inhibited this endotoxin-induced stimulation of glucose production ( P < 0.05 vs. endotoxin alone). In conclusion, sufentanil modulates the response to intravenous endotoxin by dissociating the TNF and IL-6 response, increasing insulin and catecholamine levels, and depressing the increase in glucose production. Therefore, opiates alter inflammatory, endocrine, and metabolic regulation in endotoxemia.
Effects of epinephrine on glucose metabolism in contracting rat skeletal muscles
Authors: Aslesen Rune , Jensen Jørgen
Published: December 2017

The effects of epinephrine on glucose metabolism during contractile activity and insulin stimulation were investigated in fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles from Wistar rats. All muscles were mounted on contraction apparatuses, and some muscles were stimulated electrically for 30 min in vitro. Glucose uptake and glucose phosphorylation were measured with 2-[1,2-3H(N)]deoxy-d-glucose and glucose transport with 3- O-[ methyl-3H]methyl-d-glucose.d-[1-14C]mannitol was used to correct for extracellular space. In epitrochlearis, both contraction and insulin increased glucose transport by threefold, and combined they showed an additive effect. Epinephrine (10−6M) did not influence glucose transport across the membrane during contractile activity or insulin stimulation. In the absence of epinephrine, similar glucose phosphorylation was obtained during contraction and during insulin stimulation in epitrochlearis (∼12 mmol ⋅ kg dry wt−1⋅ 30 min−1). In the presence of epinephrine, 9.5 ± 0.6 mmol ⋅ kg dry wt−1⋅ 30 min−1glucose was phosphorylated during contraction, whereas only 2.0 ± 0.3 mmol ⋅ kg dry wt−1⋅ 30 min−1was phosphorylated during insulin stimulation ( P < 0.01), despite a similar glucose 6-phosphate concentration. Comparable results were obtained in soleus. In conclusion, our data suggest that epinephrine inhibits glucose phosphorylation much less during contraction than during insulin stimulation.
Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids
Authors: Roemmich James N. , Clark Pamela A. , Berr Stuart S. , Mai Vu , Mantzoros Christos S. , Flier Jeffrey S. , Weltman Arthur , Rogol Alan D.
Published: December 2017

Little is known about the influence of adiposity and hormone release on leptin levels in children and adolescents. We utilized criterion methods to examine the relationships among sex steroids, body composition (4 compartment), abdominal visceral and subcutaneous fat (magnetic resonance imagery), total subcutaneous fat (sum of 9 skinfolds), energy expenditure (doubly labeled water), aerobic fitness, and serum leptin levels in prepubertal and pubertal boys ( n = 16; n = 13) and girls ( n = 12; n = 15). The sum of skinfolds accounted for more variance in leptin levels of all girls [coefficient of determination ( R 2) = 0.70, P < 0.001] and all boys ( R 2 = 0.60, P < 0.001) than the total fat mass (girls, R 2 = 0.52, P < 0.001; boys, R 2 = 0.23, P < 0.001). Total energy expenditure, corrected for the influence of fat-free mass, correlated inversely with leptin ( R 2 = 0.18, P = 0.02). Gender differences in leptin disappeared when corrected for sex steroid levels or the combination of adiposity and energy expenditure. In multiple regression, the sum of skinfolds and free testosterone and estrogen levels accounted for 74% of the variance in leptin levels. We conclude that serum leptin levels are positively related to subcutaneous adiposity but negatively related to androgen levels. Energy expenditure may be negatively related to leptin levels by reduction of the adiposity, or a common genetic factor may influence both the activity and serum leptin levels.
Dual mode of action of glucose pentaacetates on hormonal secretion from the isolated perfused rat pancreas
Authors: Leclercq-Meyer Viviane , Malaisse Willy J.
Published: December 2017

Isolated perfused rat pancreases were exposed, in the presence of 10.0 mMl-leucine, to either α-d-glucose pentaacetate, β-l-glucose pentaacetate, or unesterified d-glucose, all tested at a 1.7 mM concentration. The pentaacetate ester of α-d-glucose and, to a lesser extent, that of β-l-glucose stimulated both insulin and somatostatin release, whereas unesterifiedd-glucose failed to do so. In the case of insulin output, the two esters differed from one another not solely by the magnitude of the secretory response but also by its time course and reversibility. Compared with these data, the most salient difference found in the case of somatostatin release consisted of the absence of an early secretory peak in response to α-d-glucose pentaacetate administration and the higher paired ratio between the secretory responses evoked by the esters of glucose and by unesterifiedd-glucose (5.5 mM) administered at the end of the experiments. The two esters provoked an initial and short-lived stimulation of glucagon secretion, in sharp contrast to the immediate inhibitory action of unesterifiedd-glucose. Thereafter, α-d-glucose pentaacetate, but not β-l-glucose pentaacetate, caused inhibition of glucagon release, such an effect being reversed when the administration of the ester was halted. These findings indicate a dual mode of action of glucose pentaacetate esters on hormonal secretion from the endocrine pancreas. The intracellular hydrolysis of α-d-glucose pentaacetate and subsequent catabolism of its hexose moiety may contribute to the early peak-shaped insulin response to this ester, to the persistence of a positive secretory effect in B and D cells after cessation of its administration, and to the late inhibition of glucagon release. However, a direct effect of the esters themselves, by some as-of-yet unidentified coupling process, is postulated to account for the stimulation of insulin and somatostatin release by β-l-glucose pentaacetate and for the initial enhancement of glucagon secretion provoked by both glucose esters.
Smaller differences in total and regional adiposity with age in women who regularly perform endurance exercise
Authors: Van Pelt Rachael E. , Davy Kevin P. , Stevenson Edie T. , Wilson Teresa M. , Jones Pamela P. , Desouza Christopher A. , Seals Douglas R.
Published: December 2017

Our aim was to determine if women who regularly perform endurance exercise demonstrate age-related elevations in body mass and adiposity. Ninety-five healthy females were studied: premenopausal ( n = 28; mean ± SE age 30 ± 1 yr) and postmenopausal ( n = 31; 56 ± 1 yr) endurance-trained runners and premenopausal ( n = 17; 29 ± 1 yr) and postmenopausal ( n = 19; 61 ± 1 yr) sedentary controls. In the runners, body mass did not differ across age, but percent fat and fat mass were higher ( P < 0.05) in the postmenopausal women. The age-related difference in total body fat, however, was only ∼50% as great ( P < 0.01) as that observed in the sedentary controls due in part to smaller age-related differences in central (truncal) fat. The higher fat mass in the postmenopausal runners was modestly (inversely) related to both exercise volume ( r = −0.44, P < 0.01) and maximal oxygen consumption ( r = −0.41, P < 0.01). The present findings provide experimental support for the hypothesis that women who regularly engage in vigorous endurance exercise may not gain body weight, undergo only a modest increase in total body fat, and do not demonstrate a significant elevation in central adiposity with age.
Effect of fentanyl on morphine levels in the brain in rats receiving intracerebroventricular injection of TNF-α
Authors: Shirouzu Yuichirou , Shirouzu Kazuo , Yoshida Shogo
Published: December 2017

Fentanyl citrate analgesia attenuates the excess nitrogen excretion in the urine and glucose production induced by trauma. On the other hand, intracerebroventricular injection of morphine stimulates excretion of stress hormones, such as catecholamines and corticosterone. Furthermore, morphine levels in the brain are increased during fasting and sepsis. The aims of this study were to determine whether intracerebroventricular injection of tumor necrosis factor-α (TNF-α) elevates morphine levels in the rat brain and whether prophylactic administration of fentanyl blocks metabolic responses induced by intracerebroventricular injection of TNF-α because of a reduction of morphine levels in the brain. Morphine levels in the brain were increased from 648 to 1,134 fmol/g at 30 min after intracerebroventricular injection of TNF-α ( P < 0.05 vs. control). This increase was associated with an increase in stress hormones (corticosterone: 416.1 ± 69.1 ng/ml, P < 0.05 vs. control; epinephrine: 3,778.3 ± 681.3 pg/ml, P < 0.01 vs. control) and an enhancement of proteolysis (254.2 ± 45.7 μmol Leu ⋅ kg−1⋅ h−1, P < 0.01 vs. control) and glucose production (7.5 ± 0.7 mg ⋅ kg−1⋅ min−1, P < 0.05 vs. control). Fentanyl reduced morphine levels in the brain to 624 fmol/g (not significant vs. control), resulting in a reduction of stress hormone levels in the plasma and blunted metabolic responses. In conclusion, prophylactic administration of fentanyl prevented an increase in morphine levels in the brain induced by intracerebroventricular injection of TNF-α, leading to a reduction in stress hormone levels and subsequent metabolic responses.
Mechanisms of glucose intolerance during triglyceride infusion
Authors: Rigalleau V. , Beylot M. , Pachiaudi C. , Guillot C. , Deleris G. , Gin H.
Published: December 2017

Lipid infusions may affect glucose tolerance by effects on glucose production or utilization. We performed double-labeled oral glucose tolerance tests with and without a lipid infusion in eight normal subjects. During the lipid infusion, plasma glucose and insulin levels were higher, showing some insulin resistance. The increased glucose level was due to a higher total glucose appearance rate, partly reproducible by a control infusion of glycerol [saline 1,181 ± 71 mg ⋅ kg−1 ⋅ 330 min−1 vs. lipid 1,388 ± 100 ( P < 0.05) vs. glycerol 1,276 ± 126 (NS)]. The tracer-determined appearance rate of exogenous glucose was higher with lipid infusion but was probably overestimated because of higher13C recycling into glucose. Residual systemic glucose production was increased but was reproducible by the glycerol infusion. Total glucose disposal was increased. This was observed despite a lower stimulation of total glucose oxidation as measured by indirect calorimetry, whereas oxidation of exogenous glucose was normal after correction for the lipid-induced modification of excretion rate of13CO2. Accordingly, glucose nonoxidative disposal was increased. These moderate modifications of glucose metabolism (increased appearance, increased nonoxidative disposal, and lower total oxidation) have been reported in starvation-induced or spontaneously impaired glucose tolerance. Further impairment, especially decreased nonoxidative glucose disposal, seems to be required to produce non-insulin-dependent diabetes mellitus.
Effect of dietary protein on translation initiation in rat skeletal muscle and liver
Authors: Yoshizawa Fumiaki , Kimball Scot R. , Vary Thomas C. , Jefferson Leonard S.
Published: December 2017

The effect of dietary protein on the initiation of mRNA translation was examined in rats starved for 18 h and then fed isocaloric diets containing either 20% protein (20P) or no added protein (0P). Feeding the 20P diet, but not the 0P diet, stimulated protein synthesis in skeletal muscle and liver by 38 and 41%, respectively. The stimulation was associated with reduced binding of eukaryotic initiation factor (eIF) 4E to the translational repressor 4E-BP1, increased formation of the active eIF4E-eIF4G complex, and increased phosphorylation of 4E-BP1. In contrast, feeding a 0P diet had no effect on any of these parameters. Feeding a 20P diet resulted in partial dephosphorylation of eIF4E in both tissues. In liver, refeeding a 0P diet also resulted in partial eIF4E dephosphorylation, suggesting that the phosphorylation state of eIF4E is not important in the stimulation of protein synthesis under these conditions. Finally, plasma insulin concentrations were the same in rats fed either diet (14.8 ± 4.9 vs. 15.5 ± 4.5 μU/ml for 20P and 0P groups, respectively), suggesting that feeding-induced changes in plasma insulin are not sufficient to stimulate protein synthesis. Instead, a combination of dietary protein and insulin may be required to stimulate translation initiation.
Whole body, adipose tissue, and forearm norepinephrine kinetics in lean and obese women
Authors: Coppack Simon W. , Horowitz Jeffrey F. , Paramore Deanna S. , Cryer Philip E. , Royal Henry D. , Klein Samuel
Published: December 2017

We evaluated whole body and regional (subcutaneous abdominal adipose tissue and forearm) norepinephrine (NE) kinetics in seven lean (body mass index 21.3 ± 0.5 kg/m2) and six upper body obese (body mass index 36.4 ± 0.4 kg/m2) women who were matched on fat-free mass. NE kinetics were determined by infusing [3H]NE and obtaining blood samples from a radial artery, a deep forearm vein draining mostly skeletal muscle, and an abdominal vein draining subcutaneous abdominal fat. Mean systemic NE spillover tended to be higher in obese (2.82 ± 0.49 nmol/min) than in lean (2.53 ± 0.40 nmol/min) subjects, but the differences were not statistically significant. Adipose tissue and forearm NE spillover rates into plasma were greater in lean (0.91 ± 0.08 pmol ⋅ 100 g tissue−1 ⋅ min−1and 1.01 ± 0.09 pmol ⋅ 100 ml tissue−1 ⋅ min−1, respectively) than in obese (0.26 ± 0.05 pmol ⋅ 100 g tissue−1 ⋅ min−1and 0.58 ± 0.11 pmol ⋅ 100 ml tissue−1 ⋅ min−1, respectively) subjects ( P < 0.01). These results demonstrate that adipose tissue is an active site for NE metabolism in humans. Adipose tissue NE spillover is considerably lower in obese than in lean women, which may contribute to the lower rate of lipolysis per kilogram of fat mass observed in obesity.
Muscle contraction increases palmitate esterification and oxidation and triacylglycerol oxidation
Authors: Dyck D. J. , Bonen A.
Published: December 2017

We examined the oxidation and esterification of palmitate and the hydrolysis and oxidation of intramuscular lipids in isolated soleus muscles at rest and during tetanic contractions (2–40 tetani/min). Muscles were pulsed with [14C]palmitate to prelabel all intramuscular lipid pools. Muscles remained at rest or were then stimulated to contract at 2, 8, 20, or 40 tetani/min (30 min) in the presence of [3H]palmitate. Palmitate oxidation was increased 412% at 2 tetani/min ( P < 0.05) and 880% at 8 tetani/min ( P < 0.05). During contraction there was an absolute increase in esterification of palmitate to triacylglycerol in proportion with the increasing rate of palmitate oxidation. Intramuscular lipid oxidation provided ∼77% of the total muscle energy compared with ∼3% provided by exogenous palmitate under all conditions, with carbohydrate sources (glycogen and glucose) providing ∼20% of the total energy. Thus, during muscle contraction, the oxidation rates of both exogenous and intramuscular lipids are increased in proportion to each other, while concomitantly palmitate is esterified in proportion to its oxidation.
The inhibition of gluconeogenesis following alcohol in humans
Authors: Siler Scott Q. , Neese Richard A. , Christiansen Mark P. , Hellerstein Marc K.
Published: December 2017

Accurate quantification of gluconeogenic flux following alcohol ingestion in overnight-fasted humans has yet to be reported. [2-13C1]glycerol, [U-13C6]glucose, [1-2H1]galactose, and acetaminophen were infused in normal men before and after the consumption of 48 g alcohol or a placebo to quantify gluconeogenesis, glycogenolysis, hepatic glucose production, and intrahepatic gluconeogenic precursor availability. Gluconeogenesis decreased 45% vs. the placebo (0.56 ± 0.05 to 0.44 ± 0.04 mg ⋅ kg−1 ⋅ min−1vs. 0.44 ± 0.05 to 0.63 ± 0.09 mg ⋅ kg−1 ⋅ min−1, respectively, P < 0.05) in the 5 h after alcohol ingestion, and total gluconeogenic flux was lower after alcohol compared with placebo. Glycogenolysis fell over time after both the alcohol and placebo cocktails, from 1.46–1.47 mg ⋅ kg−1 ⋅ min−1to 1.35 ± 0.17 mg ⋅ kg−1 ⋅ min−1(alcohol) and 1.26 ± 0.20 mg ⋅ kg−1 ⋅ min−1, respectively (placebo, P < 0.05 vs. baseline). Hepatic glucose output decreased 12% after alcohol consumption, from 2.03 ± 0.21 to 1.79 ± 0.21 mg ⋅ kg−1 ⋅ min−1( P < 0.05 vs. baseline), but did not change following the placebo. Estimated intrahepatic gluconeogenic precursor availability decreased 61% following alcohol consumption ( P < 0.05 vs. baseline) but was unchanged after the placebo ( P < 0.05 between treatments). We conclude from these results that gluconeogenesis is inhibited after alcohol consumption in overnight-fasted men, with a somewhat larger decrease in availability of gluconeogenic precursors but a smaller effect on glucose production and no effect on plasma glucose concentrations. Thus inhibition of flux into the gluconeogenic precursor pool is compensated by changes in glycogenolysis, the fate of triose-phosphates, and peripheral tissue utilization of plasma glucose.
Hypokalemia alters sex hormone and gonadotropin levels: evidence that FSH may be required for luteinization
Authors: Tejada Francisco , Cremades Asunción , Avilés Manuel , Castells Maria T. , Peñafiel Rafael
Published: December 2017

Hypokalemia produced different effects on steroid sex hormone concentrations in plasma and ovary in the mouse. Estradiol levels were slightly increased, whereas circulating progesterone was markedly decreased in all estrous periods. The preovulatory surge of gonadotropins and the secondary surge of follicle-stimulating hormone (FSH) at estrus were also decreased, but basal levels of both gonadotropins were unaffected. Supplementation with luteinizing hormone (LH), FSH, or gonadotropin-releasing hormone (GnRH) at proestrus rapidly normalized plasma and ovarian progesterone levels at this stage of the estrous cycle. Plasma progesterone levels at diestrus were restored only by combined treatment, at the periovulatory stage, with LH and FSH or GnRH but not by LH or FSH alone. The results demonstrate a lack of steroidogenic activity in the corpus luteum of the potassium-deficient mice and, furthermore, that FSH plays an important role in luteinization in the hypokalemic mice. We conclude that alteration of the transcellular potassium gradient may affect the regulation of the periovulatory surge of gonadotropins and progesterone secretion, probably by altering the release of GnRH from the hypothalamus. In addition, the results suggest that FSH may play a certain role as a luteotropic hormone in mice.
Regulation of glycogen accumulation in L6 myotubes cultured under optimized differentiation conditions
Authors: Elsner Peter , Quistorff Bjørn , Hermann Thomas S. , Dich John , Grunnet Niels
Published: December 2017

The differentiation of the L6 myogenic cell line was enhanced by the addition of dexamethasone, retinoic acid, insulin-like growth factor I (IGF-I), and creatine. Spontaneous contractions appeared from day 10 or 11 and persisted to day 14 or 15. Glucose transport was increased by insulin (100 nM) and IGF-I (5 nM) by ∼60%. The highest level of glycogen was measured in myotubes differentiated under the influence of a combination of 5 nM dexamethasone, 100 nM retinoic acid, 5 nM IGF-I, and 10 mM creatine with glucose as substrate. The glycogen accumulation rate was constant from 0 to 2 h of incubation and decreased gradually to zero at 4 h. From 0 to 0.5 h of the glycogen accumulation, the glycogen synthase a(GS a) activity was 30–35% of the total activity, with a subsequent gradual decline to 2.5% after 6 h. The glycogen phosphorylase a(GPh a) activity was constant at ∼80% from 0 to 0.5 h, increasing to ∼100% after 6 h. The activity ratio of GS a to GPh a decreased about sixfold without significant change in the rate of glycogen accumulation. This indicates that factors other than phosphorylation/dephosphorylation play a decisive role in the regulation of glycogen metabolism in L6 myotubes. Intracellular glucose (glucosei) and glucose 6-phosphate (G-6- P) may be such factors. The observed values of these parameters may in fact explain an activation of GS a(G-6- P) and an inhibition of GPh a(glucosei).
Relationship of fetal alanine uptake and placental alanine metabolism to maternal plasma alanine concentration
Authors: Timmerman Michelle , Chung Misoo , Wilkening Randall B. , Fennessey Paul V. , Battaglia Frederick C. , Meschia Giacomo
Published: December 2017

Uterine and umbilical uptakes of alanine (Ala) were measured in 10 ewes before (control) and during intravenous infusion of Ala, which increased maternal arterial Ala concentration from 115 ± 14 to 629 ± 78 μM ( P < 0.001). In 8 of these ewes, placental Ala fluxes were traced by constant intravenous infusion ofl-[3,3,3-2H3]Ala in the mother andl-[1-13C]Ala in the fetus. Rates are reported as micromoles per minute per kilogram fetus. Ala infusion increased uterine uptake (2.5 ± 0.6 to 15.6 ± 3.1, P < 0.001), umbilical uptake (3.1 ± 0.5 to 6.9 ± 0.8, P < 0.001), and net uteroplacental utilization (−0.7 ± 0.8 to 8.6 ± 2.7, P < 0.01) of Ala. Control Ala flux to fetus from mother ( R f,m) was much less than the Ala flux to fetus from placenta ( R f,p) (0.17 ± 0.04 vs. 5.0 ± 0.6). Two additional studies utilizingl-[U-13C]Ala as the maternal tracer confirmed the small relative contribution of R f,m to R f,p. During maternal Ala infusion, R f,m increased significantly ( P < 0.02) but remained a small fraction of R f,p (0.71 ± 0.2 vs. 7.3 ± 1.3). We conclude that maternal Ala entering the placenta is metabolized and exchanged for placental Ala, so that most of the Ala delivered to the fetus is produced within the placenta. An increase in maternal Ala concentration increases placental Ala utilization and the fetal uptake of both maternal and placental Ala.
1,25-Dihydroxyvitamin D3upregulates natriuretic peptide receptor-C expression in mouse osteoblasts
Authors: Yanaka Noriyuki , Akatsuka Hiroyuki , Kawai Eri , Omori Kenji
Published: December 2017

1,25-Dihydroxyvitamin D3[1,25(OH)2D3], a key regulator of mineral metabolism, regulates expression of several genes related to bone formation. The present study examined the 1,25(OH)2D3-mediated regulation of natriuretic peptide receptor-C (NPR-C) expression in osteoblasts. 1,25(OH)2D3treatment significantly increased NPR-C-dependent atrial natriuretic peptide-binding activity and synthesis of the NPR-C protein in mouse osteoblastic cells in a cell-specific manner. Western blot analysis also demonstrated that 1,25(OH)2D3upregulated expression of NPR-C protein in slow kinetics. Next, Northern blot analysis revealed a significant increase in the steady-state NPR-C mRNA level by 1,25(OH)2D3. Sequence analysis of the 9 kb of the 5′-flanking region of the mouse NPR-C gene revealed an absence of consensus vitamin D-response elements, and promoter analysis using osteoblastic cells stably transfected with mouse NPR-C promoter-reporter constructs showed a slight increase of promoter activity with 1,25(OH)2D3treatment. In addition, a nuclear run-on assay exhibited that the transcriptional rate of the NPR-C gene was unchanged by 1,25(OH)2D3, whereas that of the osteopontin gene was increased. Evaluation of NPR-C mRNA half-life demonstrated that 1,25(OH)2D3significantly increased the NPR-C mRNA stability in osteoblastic cells. 1,25(OH)2D3attenuated intracellular cGMP production in osteoblastic cells stimulated by C-type natriuretic peptide (CNP) without a significant change of the natriuretic peptide receptor-B mRNA level, suggesting enhancement of the clearance of exogenously added CNP via NPR-C. Furthermore, NPR-C and osteopontin mRNAs in mouse calvariae were significantly increased by administration of 1,25(OH)2D3, and immunohistological analysis demonstrated that NPR-C is actually and strongly expressed in mouse periosteal fibroblasts. These findings suggest that 1,25(OH)2D3can play a critical role for determination of the natriuretic peptide availability in bones by regulation of NPR-C expression through stabilizing its mRNA.
Stimulatory effect of insulin on creatine accumulation in human skeletal muscle
Authors: Steenge G. R. , Lambourne J. , Casey A. , Macdonald I. A. , Greenhaff P. L.
Published: December 2017

This study investigated the effect of insulin on plasma and muscle creatine accumulation and limb blood flow in humans after creatine administration. Seven men underwent a 300-min euglycemic insulin clamp combined with creatine administration on four separate occasions. Insulin was infused at rates of 5, 30, 55, or 105 mU ⋅ m−2⋅ min−1, and on each occasion 12.4 g creatine was administered. During infusion of insulin at rates of 55 and 105 mU ⋅ m−2⋅ min−1, muscle total creatine concentration increased by 4.5 ± 1.4 ( P < 0.05) and 8.3 ± 1.0 mmol/kg dry mass ( P < 0.05), and plasma creatine concentrations were lower at specific time points compared with the 5 mU ⋅ m−2⋅ min−1infusion rate. The magnitude of increase in calf blood flow (plethysmography) was the same irrespective of the rate of insulin infusion, and forearm blood flow increased to the same extent as the three highest infusion rates. These findings demonstrate that insulin can enhance muscle creatine accumulation in humans but only when present at physiologically high or supraphysiological concentrations. This response is likely to be the result of an insulin-mediated increase in muscle creatine transport rather than creatine delivery.
Insulin-like growth factor I stimulates cardiac myosin heavy chain and actin synthesis in the awake rat
Authors: Young Lawrence H. , Renfu Yin , Hu Xiaoyue , Chong Sang , Hasan Syed , Jacob Ralph , Sherwin Robert S.
Published: December 2017

To determine the effect of insulin-like growth factor I (IGF-I) on cardiac contractile protein synthesis in vivo, we measuredl-[ ring-2,6-3H]phenylalanine incorporation into myosin heavy chain and actin during intravenous infusions (4 h) of either saline or IGF-I (1 μg ⋅ kg−1 ⋅ min−1) in awake rats. After an overnight fast, IGF-I increased myosin synthesis by 29% compared with saline (11.5 ± 0.8 vs. 8.9 ± 0.6%/day, P < 0.01) and actin synthesis by 26% (7.2 ± 0.3 vs. 5.7 ± 0.3%/day, P < 0.01), with similar effects in left and right ventricles and a comparable effect on mixed cardiac protein. When amino acids were infused with IGF-I, a further increase in myosin synthesis was observed ( P< 0.01). In fed rats, despite higher baseline synthesis rates than in fasted rats ( P < 0.01), IGF-I also increased the synthesis of myosin (12.3 ± 0.5 vs. 9.9 ± 0.5%/day, P < 0.01) and actin (8.8 ± 0.3 vs. 7.5 ± 0.2%/day, P < 0.01) compared with saline. IGF-I infusion had no hypoglycemic effect and did not change heart rate or blood pressure. Thus relatively low-dose IGF-I has a direct action in vivo to acutely increase heart contractile protein synthesis in both fasted and fed awake rats.
Endocrine relationships during human spaceflight
Authors: Stein T. P. , Schluter M. D. , Moldawer L. L.
Published: December 2017

Human spaceflight is associated with a chronic loss of protein from muscle. The objective of this study was to determine whether changes in urinary hormone excretion could identify a hormonal role for this loss. Urine samples were collected from the crews of two Life Sciences Space Shuttle missions before and during spaceflight. Data are means ± SE with the number of subjects in parentheses. The first value is the mean preflight measurement, and the second value is the mean inflight measurement. Adrenocorticotropic hormone (ACTH) [27.7 ± 4.4 (9) vs. 25.1 ± 3.4 (9) ng/day], growth hormone [724 ± 251 (9) vs. 710 ± 206 (9) ng/day], insulin-like growth factor I [6.81 ± 0.62 vs. 6.04 ± 0.51 (8) nM/day], and C-peptide [44.9 ± 8.3 (9) vs. 50.7 ± 10.3 (9) μg/day] were unchanged with spaceflight. In contrast, free 3,5,3′-triiodothyronine [791 ± 159 (9) vs. 371 ± 41 (9) pg/day, P < 0.05], prostaglandin E2(PGE2) [1,064 ± 391 (8) vs. 465 ± 146 (8) ng/day, P < 0.05], and its metabolite PGE-M [1,015 ± 98 (9) vs. 678 ± 105 (9) ng/day, P < 0.05] were decreased inflight. The urinary excretion of most hormones returned to their preflight levels during the postflight period, with the exception of ACTH [47.5 ± 10.3 (9) ng/day], PGE2[1,433 ± 327 (8) ng/day], PGF2α, [2,786 ± 313 (8) ng/day], and its metabolite PGF-M [4,814 ± 402 (9) ng/day], which were all increased compared with the preflight measurement ( P < 0.05). There was a trend for urinary cortisol to be elevated inflight [55.3 ± 5.9 (9) vs. 72.5 ± 11.1 μg/day, P = 0.27] and postflight [82.7 ± 8.6 (8) μg/day, P = 0.13]. The inflight human data support ground-based in vitro work showing that prostaglandins have a major role in modulating the changes in muscle protein content in response to tension or the lack thereof.
Effect of hypophysectomy on the proliferation and differentiation of rat bone marrow stromal cells
Authors: Yeh James K. , Evans Jodi F. , Chen Meng-Meng , Aloia John F.
Published: December 2017

Conditions such as estrogen deficiency, skeletal unloading, and aging have all been demonstrated to have various effects on the proliferation and differentiation of bone marrow stroma-derived osteoprogenitor cells. Here we have sought to examine the effects of pituitary hormone deficiency on the proliferation and the differentiation of these osteoprogenitor cells using the hypophysectomized (HX) rat as a model. In the present study, we use an in vitro culture system to examine the effects of HX on the osteogenic potential of rat bone marrow stroma. With the intact animal as a control, we used [3H]thymidine incorporation and cell number as indexes of proliferation. We also measured alkaline phosphatase enzyme activity, relative levels of osteocalcin expression with RT-PCR, and osteopontin and bone sialoprotein steady-state levels by Northern blot to delineate the effect on differentiation. Our results indicate that osteoprogenitor cells exposed to a pituitary hormone-deficient environment in vivo demonstrate an enhanced proliferative capacity and also exhibit an augmented expression of differentiation markers when exposed to an optimal environment in vitro.
Aldosterone release during the sleep-wake cycle in humans
Authors: Charloux Anne , Gronfier Claude , Lonsdorfer-Wolf Evelyne , Piquard François , Brandenberger Gabrielle
Published: December 2017

The aim of this study was to assess the relative influence on the 24-h aldosterone profile of the adrenocorticotropic system, primarily modulated by a circadian rhythmicity, and the renin-angiotensin system, which is influenced by sleep. Cortisol, plasma renin activity (PRA), and aldosterone were measured for 24 h in healthy subjects under basal conditions, once with nocturnal sleep and once with a night of sleep deprivation followed by 8 h of daytime sleep. The sleep period displayed high mean aldosterone levels, pulse amplitude, and frequency that were reduced during waking periods. During sleep, aldosterone pulses were mainly related to PRA oscillations, whereas they were mainly associated with cortisol pulses during waking periods. Cross-correlation analysis between sleep electroencephalographic activity in the delta band and aldosterone levels yielded significant results, aldosterone following delta waves by ∼30 min. This study demonstrates that the 24-h aldosterone profile is strongly influenced by sleep processes. A dual influence, by the renin-angiotensin system during sleep and by the adrenocorticotropic system during wakefulness, is exerted on aldosterone pulses throughout the 24-h period.
Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism
Authors: Evans Kevin , Clark Mo L. , Frayn Keith N.
Published: December 2017

We have studied the fate of lipoprotein lipase (LPL)-derived fatty acids by measuring arteriovenous differences across subcutaneous adipose tissue and skeletal muscle in vivo. Six subjects were fasted overnight and were then given 40 g of triacylglycerol either orally or as an intravenous infusion over 4 h. Intracellular lipolysis (hormone-sensitive lipase action; HSL) was suppressed after both oral and intravenous fat loads ( P < 0.001). Insulin, a major regulator of HSL activity, showed little change after either oral or intravenous fat load, suggesting that suppression of HSL action occurred independently of insulin. The rate of action of LPL (measured as triacylglycerol extraction) increased with both oral and intravenous fat loads in adipose tissue ( P = 0.002) and skeletal muscle ( P = 0.001). There was increased escape of LPL-derived fatty acids into the circulation from adipose tissue, shown by lack of reesterification of fatty acids. There was no release into the circulation of LPL-derived fatty acids from skeletal muscle. These results suggest that insulin is not essential for HSL suppression or increased triacylglycerol clearance but is important in reesterification of fatty acids in adipose tissue but not uptake by skeletal muscle, thus affecting fatty acid partitioning between adipose tissue and the circulation, postprandial nonesterified fatty acid concentrations, and hepatic very low density lipoprotein secretion.
Dexamethasone inhibits small intestinal growth via increased protein catabolism in neonatal pigs
Authors: Burrin Douglas G. , Wester Timothy J. , Davis Teresa A. , Fiorotto Marta L. , Chang Xiaoyan
Published: December 2017

Our objective was to determine how dexamethasone (Dex) affects gastrointestinal protein metabolism and growth in neonatal pigs. Two-day-old pigs were given daily subcutaneous injections of either Dex (1 mg/kg body wt, n = 7) or saline (control, n = 6) for 7 days. In vivo protein synthesis was measured after 7 days with a bolus of [3H]phenylalanine. Tissue protein contents were measured in an initial control group of 2-day-old pigs and in control and Dex pigs after 7 days to estimate protein accretion and degradation. In control pigs, the protein accretion in the ileum was nearly sixfold greater than in the jejunum during the 7-day period. Dex nominally altered stomach growth but completely blocked the accretion of protein and DNA in the jejunum and ileum, with reduced villus height in the ileum. Dex increased the fractional protein degradation rate in the ileum (28%) and decreased the absolute protein synthesis rate in the jejunum and ileum by 17 and 21%, respectively. Dex resulted in a 40% lower total intestinal lactase activity compared with controls via reductions in both specific activity and tissue mass, especially in the ileum. Dex significantly decreased the circulating concentrations of insulin-like growth factor (IGF) I and IGF-binding protein (IGFBP)-1, -2, and -3. However, the tissue abundance of the IGF-I receptor in the stomach and ileum was greater in Dex pigs than controls. Our results suggest that Dex significantly inhibits small intestinal growth via both increased degradation and decreased synthesis of protein. Furthermore, the inhibition of intestinal growth resulted in significantly decreased lactose digestive capacity.