bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences in substrate utilization during submaximal exercise in endurance-trained subjects
Authors: Roepstorff Carsten , Steffensen Charlotte H. , Madsen Marianne , Stallknecht Bente , Kanstrup Inge-Lis , Richter Erik A. , Kiens Bente
Published: February 2015

Substrate utilization across the leg during 90 min of bicycle exercise at 58% of peak oxygen uptake (V˙o2 peak) was studied in seven endurance-trained males and seven endurance-trained, eumenorrheic females by applying arteriovenous catheterization, stable isotopes, and muscle biopsies. The female and male groups were matched according toV˙o2 peakper kilogram of lean body mass, physical activity level, and training history of the subjects. All subjects consumed the same diet, well controlled in terms of nutrient composition as well as energy content, for 8 days preceding the experiment, and all females were tested in the midfollicular phase of the menstrual cycle. During exercise, respiratory exchange ratio (RER) and leg respiratory quotient (RQ) were similar in females and males. Myocellular triacylglycerol (TG) degradation was negligible in males but amounted to 12.4 ± 3.2 mmol/kg dry wt in females and corresponded to 25.0 ± 6.0 and 5.0 ± 7.3% of total oxygen uptake in females and males, respectively ( P < 0.05). Utilization of plasma fatty acids (12.0 ± 2.5 and 9.6 ± 1.5%), blood glucose (13.6 ± 1.5 and 14.3 ± 1.5%), and glycogen (48.5 ± 4.9 and 42.8 ± 2.1%) were similar in females and males. Thus, in females, measured substrate oxidation accounted for 99% of the leg oxygen uptake, whereas in males 28% of leg oxygen uptake was unaccounted for in terms of measured oxidized lipid substrates. These findings may indicate that males utilized additional lipid sources, presumably very low density lipoprotein-TG or TG located between muscle fibers. On the basis of RER and leg RQ, it is concluded that no gender difference existed in the relative contribution from carbohydrate and lipids to the oxidative metabolism across the leg during submaximal exercise at the same relative workload. However, an effect of gender appears to occur in the utilization of the different lipid sources.
Peak of circadian melatonin rhythm occurs later within the sleep of older subjects
Authors: Duffy Jeanne F. , Zeitzer Jamie M. , Rimmer David W. , Klerman Elizabeth B. , Dijk Derk-Jan , Czeisler Charles A.
Published: February 2015

We investigated the relationship between sleep timing and the timing of the circadian rhythm of plasma melatonin secretion in a group of healthy young and older subjects without sleep complaints. The timing of sleep and the phase of the circadian melatonin rhythm were earlier in the older subjects. The relationship between the plasma melatonin rhythm and the timing of sleep was such that the older subjects were sleeping and waking earlier relative to their nightly melatonin secretory episode. Consequently, the older subjects were waking at a time when they had higher relative melatonin levels, in contrast with younger subjects, whose melatonin levels were relatively lower by wake time. Our findings indicate that aging is associated not only with an advance of sleep timing and the timing of circadian rhythms but also with a change in the internal phase relationship between the sleep-wake cycle and the output of the circadian pacemaker. In healthy older subjects, the relative timing of the melatonin rhythm with respect to sleep may not play a causal role in sleep disruption.
Regulation of the human brain natriuretic peptide gene by GATA-4
Authors: He Quan , Mendez Mariela , LaPointe Margot C.
Published: February 2015

Brain natriuretic peptide (BNP) is a cardiac hormone constitutively expressed in the adult heart. We previously showed that the human BNP (hBNP) proximal promoter region from −127 to −40 confers myocyte-specific expression. The proximal hBNP promoter contains several putative cis elements. Here we tested whether the proximal GATA element plays a role in basal and inducible regulation of the hBNP promoter. The hBNP promoter was coupled to a luciferase reporter gene (1818hBNPLuc) and transferred into neonatal ventricular myocytes (NVM), and luciferase activity was measured as an index of hBNP promoter activity. Mutation of the putative GATA element at −85 of the hBNP promoter [1818(mGATA)hBNPLuc] reduced activity by 97%. To study transactivation of the hBNP promoter, we co-transfected 1818hBNPLuc with the GATA-4 expression vector. GATA-4 activated 1818hBNPLuc, and this effect was eliminated by mutation of the proximal GATA element. Electrophoretic mobility shift assay showed that an oligonucleotide containing the hBNP GATA motif bound to cardiomyocyte nuclear protein, which was competed for by a consensus GATA oligonucleotide but not a mutated hBNP GATA element. The β-adrenergic agonist isoproterenol and its second messenger cAMP stimulated hBNP promoter activity and binding of nuclear protein to the proximal GATA element. Thus the GATA element in the proximal hBNP promoter is involved in both basal and inducible transcriptional regulation in cardiac myocytes.
Thyroid hormones and the mRNA of the GH receptor and IGFs in skeletal muscle of fetal sheep
Authors: Forhead A. J. , Li J. , Gilmour R. S. , Dauncey M. J. , Fowden A. L.
Published: February 2015

Thyroid hormones are required for the normal development of skeletal muscle in utero, although their mechanism of action is poorly understood. The present study examined the effects of the thyroid hormones on the gene expression of the growth hormone receptor (GHR) and the insulin-like growth factors (IGFs) IGF-I and IGF-II, in skeletal muscle of fetal sheep during late gestation (term 145 ± 2 days) and after manipulation of plasma thyroid hormone concentration. Thyroidectomy at 105–110 days of gestation suppressed muscle GHR and IGF-I gene expression in fetuses studied at 127–130 and 142–145 days. Muscle GHR mRNA abundance remained unchanged with increasing gestational age in intact and thyroidectomized fetuses. In the intact fetuses, a decrease in muscle IGF-I gene expression was observed between 127–130 and 142–145 days, which coincided with the normal prepartum surges in plasma cortisol and triiodothyronine (T3). At 127–130 days, downregulation of muscle IGF-I mRNA abundance was induced prematurely in intact fetuses by an infusion of cortisol for 5 days (2–3 mg · kg−1· day−1iv), which increased plasma cortisol and T3concentrations to values seen near term. However, increasing plasma T3alone by an infusion of T3for 5 days (8–12 μg · kg−1· day−1iv) in intact fetuses at this age had no effect on GHR or IGF-I gene expression in skeletal muscle. In the thyroidectomized fetuses, no additional change in the low level of muscle IGF-I mRNA abundance was seen with increasing gestational age, but at 127–130 days, IGF-I gene expression was reduced further when plasma cortisol and T3concentrations were increased by exogenous cortisol infusion. Muscle IGF-II mRNA abundance was not affected by thyroidectomy, gestational age, or exogenous hormone infusion. These findings show, in the sheep fetus, that thyroid hormones may influence the growth and development of skeletal muscle via changes in the local activity of the somatotrophic axis.
Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients
Authors: Blomqvist G. , Alvarsson M. , Grill V. , Von Heijne G. , Ingvar M. , Thorell J. O. , Stone-Elander S. , Widén L. , Ekberg K.
Published: February 2015

Using R-β-[1-11C]hydroxybutyrate and positron emission tomography, we studied the effect of acute hyperketonemia (range 0.7–1.7 μmol/ml) on cerebral ketone body utilization in six nondiabetic subjects and six insulin-dependent diabetes mellitus (IDDM) patients with average metabolic control (HbA1c = 8.1 ± 1.7%). An infusion of unlabeled R-β-hydroxybutyrate was started 1 h before the bolus injection of R-β-[1-11C]hydroxybutyrate. The time course of the radioactivity in the brain was measured during 10 min. For both groups, the utilization rate of ketone bodies was found to increase nearly proportionally with the plasma concentration of ketone bodies (1.0 ± 0.3 μmol/ml for nondiabetic subjects and 1.3 ± 0.3 μmol/ml for IDDM patients). No transport of ketone bodies from the brain could be detected. This result, together with a recent study of the tissue concentration of R-β-hydroxybutyrate in the brain by magnetic resonance spectroscopy, indicate that, also at acute hyperketonemia, the rate-limiting step for ketone body utilization is the transport into the brain. No significant difference in transport and utilization of ketone bodies could be detected between the nondiabetic subjects and the IDDM patients.
High carbohydrate availability increases LCFA uptake and decreases LCFA oxidation in perfused muscle
Authors: Turcotte Lorraine P. , Swenberger Jason R. , Yee Alice J.
Published: February 2015

To determine whether changes in long-chain fatty acid (LCFA) oxidative metabolism induced by elevated intracellular carbohydrate availability are due to changes in LCFA uptake or in mitochondrial transport capacity, rat hindquarters were perfused with 500 μM palmitate and [1-14C]palmitate or [1-14C]octanoate as well as with either low (LG) or high (HG) carbohydrate availability. Glucose uptake was higher in the HG vs. LG group (23.6 ± 1.5 vs 4.7 ± 0.9 μmol · g−1· h−1, P < 0.05). Palmitate delivery was not significantly different between groups and averaged 97.1 ± 4.6 nmol · min−1· g−1( P > 0.05). Fractional and total palmitate uptake values were 60% higher ( P < 0.05) in the HG (0.125 ± 0.012 and 7.4 ± 1.2 nmol · min−1· g−1) vs. LG (0.079 ± 0.009 and 11.8 ± 1.5 nmol · min−1· g−1) group. Values of percent and total palmitate oxidized were significantly lower ( P < 0.05) in the HG (9.1 ± 1.1% and 1.31 ± 0.16 nmol · min−1· g−1) vs. LG (23.4 ± 5.2% and 0.76 ± 0.08 nmol · min−1· g−1) group. Conversely, values of fractional uptake and percent oxidation of octanoate were not significantly different between groups ( P > 0.05). Malonyl-CoA levels were inversely correlated with LCFA oxidation ( P < 0.05). These results demonstrate that high carbohydrate availability in muscle is associated with a decrease in LCFA oxidation that is not due to a parallel decrease in LCFA uptake; rather, the decrease in LCFA oxidation could be due to malonyl-CoA inhibition of mitochondrial LCFA transport.
Insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonatal pigs
Authors: O'Connor Pamela M. J. , Bush Jill A. , Suryawan Agus , Nguyen Hanh V. , Davis Teresa A.
Published: February 2015

Infusion of physiological levels of insulin and/or amino acids reproduces the feeding-induced stimulation of muscle protein synthesis in neonates. To determine whether insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonates, insulin secretion was blocked with somatostatin in fasted 7-day-old pigs ( n = 8–12/group) while glucose and glucagon were maintained at fasting levels and insulin was infused to simulate either less than fasting, fasting, intermediate, or fed insulin levels. At each dose of insulin, amino acids were clamped at either the fasting or fed level; at the highest insulin dose, amino acids were also reduced to less than fasting levels. Skeletal muscle protein synthesis was measured using a flooding dose ofl-[4-3H]phenylalanine. Hyperinsulinemia increased protein synthesis in skeletal muscle during hypoaminoacidemia and euaminoacidemia. Hyperaminoacidemia increased muscle protein synthesis during hypoinsulinemia and euinsulinemia. There was a dose-response effect of both insulin and amino acids on muscle protein synthesis. At each insulin dose, hyperaminoacidemia increased muscle protein synthesis. The effects of insulin and amino acids on muscle protein synthesis were largely additive until maximal rates of protein synthesis were achieved. Amino acids enhanced basal protein synthesis rates but did not enhance the sensitivity or responsiveness of muscle protein synthesis to insulin. The results suggest that insulin and amino acids independently stimulate protein synthesis in skeletal muscle of the neonate.
No apparent suppression by insulin of in vivo skeletal muscle lipolysis in nonobese women
Authors: Moberg Erik , Sjöberg Stefan , Hagström-Toft Eva , Bolinder Jan
Published: February 2015

To investigate the antilipolytic effect of insulin in skeletal muscle and adipose tissue in vivo, the rates of glycerol release from the two tissues were compared in 10 nonobese women during a two-step euglycemic hyperinsulinemic clamp. Tissue interstitial glycerol levels were determined by microdialysis, and tissue blood flow was assessed with the 133Xe clearance technique. Absolute rates of glycerol release were estimated according to Fick's principle. In both adipose tissue and muscle, glycerol levels decreased significantly already during the low insulin infusion rate. The fractional release of glycerol (difference between interstitial glycerol and arterialized venous plasma glycerol) was reduced by more than one-half in adipose tissue ( P < 0.0001) in response to insulin, whereas it remained unaltered in skeletal muscle. Muscle blood flow rates increased by 60% ( P < 0.02) during insulin infusion; in adipose tissue, blood flow rates did not change significantly in response to insulin. The basal rate of glycerol release from skeletal muscle amounted to ∼15% of that from adipose tissue. After insulin infusion, the rate of adipose tissue glycerol release was markedly suppressed, whereas in skeletal muscle the rate of glycerol mobilization did not change significantly in response to insulin. It is concluded that insulin does not inhibit the rate of lipolysis in skeletal muscle of nonobese women.
Mitochondrial biogenesis during skeletal muscle regeneration
Authors: Duguez Stéphanie , Féasson Léonard , Denis Christian , Freyssenet Damien
Published: February 2015

Myogenesis requires energy production for the execution of a number of regulatory and biosynthesis events. We hypothesized that mitochondrial biogenesis would be stimulated during skeletal muscle regeneration. Tibialis anterior muscles of male Sprague-Dawley rats were injected with 0.75% bupivacaine and removed at 3, 5, 7, 10, 14, 21, or 35 days after injection ( n = 5–7/group). Two main periods emerged from the histochemical analyses of muscle sections and the expression of proliferating cell nuclear antigen, desmin, and creatine phosphokinase: 1) activation/proliferation of satellite cells ( days 3–14) and 2) differentiation into muscle fibers ( days 5–35). The onset of muscle differentiation was accompanied by a marked stimulation of mitochondrial biogenesis, as indicated by a nearly fivefold increase in citrate synthase activity and state 3 rate of respiration between days 5 and 10. Peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) mRNA level and mitochondrial transcription factor A (mtTFA) protein level peaked on day 10 concurrently with the state 3 rate of respiration. Therefore, transcriptional activation by PGC-1 and mtTFA may be one of the mechanisms regulating mitochondrial biogenesis in regenerating skeletal muscle. Taken together, our results suggest that mitochondrial biogenesis may be an important regulatory event during muscle regeneration.
Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis
Authors: Trappe T. A. , White F. , Lambert C. P. , Cesar D. , Hellerstein M. , Evans W. J.
Published: February 2015

We examined the effect of two commonly consumed over-the-counter analgesics, ibuprofen and acetaminophen, on muscle protein synthesis and soreness after high-intensity eccentric resistance exercise. Twenty-four males (25 ± 3 yr, 180 ± 6 cm, 81 ± 6 kg, and 17 ± 8% body fat) were assigned to one of three groups that received either the maximal over-the-counter dose of ibuprofen (IBU; 1,200 mg/day), acetaminophen (ACET; 4,000 mg/day), or a placebo (PLA) after 10–14 sets of 10 eccentric repetitions at 120% of concentric one-repetition maximum with the knee extensors. Postexercise (24 h) skeletal muscle fractional synthesis rate (FSR) was increased 76 ± 19% ( P < 0.05) in PLA (0.058 ± 0.012%/h) and was unchanged ( P > 0.05) in IBU (35 ± 21%; 0.021 ± 0.014%/h) and ACET (22 ± 23%; 0.010 ± 0.019%/h). Neither drug had any influence on whole body protein breakdown, as measured by rate of phenylalanine appearance, on serum creatine kinase, or on rating of perceived muscle soreness compared with PLA. These results suggest that over-the-counter doses of both ibuprofen and acetaminophen suppress the protein synthesis response in skeletal muscle after eccentric resistance exercise. Thus these two analgesics may work through a common mechanism to influence protein metabolism in skeletal muscle.
Regional muscle and adipose tissue amino acid metabolism in lean and obese women
Authors: Patterson Bruce W. , Horowitz Jeffrey F. , Wu Guoyao , Watford Malcolm , Coppack Simon W. , Klein Samuel
Published: February 2015

The effect of obesity on regional skeletal muscle and adipose tissue amino acid metabolism is not known. We evaluated systemic and regional (forearm and abdominal subcutaneous adipose tissue) amino acid metabolism, by use of a combination of stable isotope tracer and arteriovenous balance methods, in five lean women [body mass index (BMI) <25 kg/m2] and five women with abdominal obesity (BMI 35.0–39.9 kg/m2; waist circumference >100 cm) who were matched on fat-free mass (FFM). All subjects were studied at 22 h of fasting to ensure that the subjects were in net protein breakdown during this early phase of starvation. Leucine rate of appearance in plasma (an index of whole body proteolysis), expressed per unit of FFM, was not significantly different between lean and obese groups (2.05 ± 0.18 and 2.34 ± 0.04 μmol · kg FFM−1· min−1, respectively). However, the rate of leucine release from forearm and adipose tissues in obese women (24.0 ± 4.8 and 16.6 ± 6.5 nmol · 100 g−1· min−1, respectively) was lower than in lean women (66.8 ± 10.6 and 38.6 ± 7.0 nmol · 100 g−1· min−1, respectively; P < 0.05). Approximately 5–10% of total whole body leucine release into plasma was derived from adipose tissue in lean and obese women. The results of this study demonstrate that the rate of release of amino acids per unit of forearm and adipose tissue at 22 h of fasting is lower in women with abdominal obesity than in lean women, which may help obese women decrease body protein losses during fasting. In addition, adipose tissue is a quantitatively important site for proteolysis in both lean and obese subjects.
Upregulation of acyl-CoA:cholesterol acyltransferase in chronic renal failure
Authors: Liang Kaihui , Vaziri N. D.
Published: February 2015

Chronic renal failure (CRF) is associated with profound abnormalities of lipid metabolism and accelerated arteriosclerotic cardiovascular disease. In a recent study, we found marked downregulation of hepatic lecithin-cholesterol acyltransferase, or LCAT, expression, which can account for impaired HDL maturation and depressed HDL cholesterol concentration in CRF. Here, we report on the effect of CRF on acyl-CoA:cholesterol acyltransferase (ACAT) expression. ACAT is an intracellular enzyme that catalyzes esterification of free cholesterol to cholesterol ester for storage or secretion. ACAT plays a major role in hepatic production and release of VLDL, intestinal absorption of cholesterol, foam cell formation, and atherogenesis. We examined hepatic expression of ACAT-1 and ACAT-2 mRNA (Northern blot) and protein (Western blot) abundance and total ACAT activity in male CRF rats (6 wk after 5/6 nephrectomy) and sham-operated controls. The CRF animals showed a significant reduction in creatinine clearance, marked hypertriglyceridemia, modest hypercholesterolemia, and significant upregulation of hepatic tissue ACAT-2 protein and mRNA abundance. In contrast, hepatic ACAT-1 mRNA and protein abundance were unaffected by CRF. Upregulation of ACAT-2 expression was accompanied by a significant increase in hepatic ACAT activity and a significant decrease in hepatic microsomal and whole liver free cholesterol concentration. Thus CRF results in significant upregulation of hepatic ACAT-2 (but not ACAT-1) expression and ACAT activity, which may, in part, contribute to the associated lipid disorders.
Regional myocardial blood flow and glucose utilization during fasting and physiological hyperinsulinemia in humans
Authors: Iozzo Patricia , Chareonthaitawee Panithaya , Di Terlizzi Marco , Betteridge D. John , Ferrannini Ele , Camici Paolo G.
Published: February 2015

We investigated the effect of insulin on total and regional myocardial blood flow (MBF) and glucose uptake (MGU) in healthy subjects (50 ± 5 yr) by means of positron emission tomography (PET) with oxygen-15-labeled water (H2 15O) and fluorine-18 labeled fluorodeoxyglucose (18FDG) before and during physiological hyperinsulinemia (40 mU · min−1 · m−2). Twelve male subjects were included in the study. During hyperinsulinemia, MBF increased from 0.91 ± 0.28 to 1.01 ± 0.31 ml · min−1 · g−1 ( n= 7 patients, P = 0.05; n = 112 regions, P < 0.005). Intersubject variability ranged from −3.0 to +41%. MGU increased from 0.11 ± 0.08 ( n = 5) to 0.56 ± 0.08 μmol · min−1 · g−1( P < 0.0001, n = 7). MBF and insulin-mediated MGU were higher in the septum and anterior and lateral wall along short-axis regions of the heart. During hyperinsulinemia, MBF was also higher in the apex and midventricle compared with the base. MBF and MGU were positively correlated before ( r = 0.66, P < 0.0001) and during hyperinsulinemia ( r= 0.24, P < 0.05). These results provide evidence that insulin stimulates MBF in normal human hearts and appears to involve mainly those regions of the heart where insulin-mediated MGU is higher. Furthermore, regional distribution of insulin-stimulated MBF and MGU does not appear to be uniform across the left ventricular wall of healthy subjects.
COX-2 inhibition attenuates anorexia during systemic inflammation without impairing cytokine production
Authors: Johnson Paulette M. , Vogt Sherri K. , Burney Mary W. , Muglia Louis J.
Published: February 2015

Anorexia and weight loss are frequent complications of acute and chronic infections and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. Selective attenuation of the hypophagic response to infection and maintenance of the production of factors essential for infection control would be a useful addition to antimicrobial therapy in the treatment of human disease. Here, we evaluate the relative contribution of cyclooxygenase (COX)-1- and COX-2-derived prostaglandins to anorexia and weight loss precipitated by systemic immune activation by lipopolysaccharide (LPS). Using COX isoform-selective pharmacological inhibitors and gene knockout mice, we found that COX-2 inhibition during LPS-induced inflammation results in preserved food intake and maintenance of body weight, whereas COX-1 inhibition results in augmented and prolonged weight loss. Regulation of neuropeptide Y, corticotropin-releasing hormone, leptin, and interleukin-6 does not change as a function of COX-2 inhibition after LPS administration. Our data implicate COX-2 inhibition as a therapeutic target to maintain nutritional status while still allowing a normal cytokine response during infection.
Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators
Authors: Joost Hans-Georg , Bell Graeme I. , Best James D. , Birnbaum Morris J. , Charron Maureen J. , Chen Y. T. , Doege Holger , James David E. , Lodish Harvey F. , Moley Kelle H. , Moley Jeffrey F. , Mueckler Mike , Rogers Suzanne , Schürmann Annette , Seino Susumu , Thorens Bernard
Published: February 2015

The recent identification of several additional members of the family of sugar transport facilitators (gene symbol SLC2A, protein symbol GLUT) has created a heterogeneous and, in part, confusing nomenclature. Therefore, this letter provides a summary of the family members and suggests a systematic nomenclature for SLC2A and GLUT symbols.
Proteolysis-inducing factor differentially influences transcriptional regulation in endothelial subtypes
Authors: Watchorn T. M. , Waddell I. , Ross J. A.
Published: February 2015

Proteolysis-inducing factor (PIF) is a novel sulfated glycoprotein initially identified as a protein capable of triggering muscle proteolysis during the process of cancer cachexia. Only skeletal muscle and liver exhibit substantial binding of PIF in adult tissue. Here, we demonstrate that PIF induces transcriptional regulation in both the liver endothelial cell line SK-HEP-1 and in human umbilical vein endothelial cells (HUVECs) but not in pulmonary artery endothelial cells. PIF differentially induces activation of nuclear factor-κB, resulting in the induction of proinflammatory cytokines [interleukin (IL)-8 and IL-6] and increased expression of the cell surface proteins intercellular adhesion molecule-1 and vascular cell adhesion molecule in SK-HEP-1 and HUVECs only. In addition, PIF induces the shedding of syndecans from the cell surface. Syndecans are involved in wound repair, metastasis of cancers, and embryonic development. These results suggest that PIF may play additional roles in the proinflammatory response observed in cancer cachexia but may also have a role without the cachectic process.
Insulin induces the translocation of the fatty acid transporter FAT/CD36 to the plasma membrane
Authors: Luiken Joost J. F. P. , Dyck David J. , Han Xiao-Xia , Tandon Narendra N. , Arumugam Yoga , Glatz Jan F. C. , Bonen Arend
Published: February 2015

It is well known that muscle contraction and insulin can independently translocate GLUT-4 from an intracellular depot to the plasma membrane. Recently, we have shown that the fatty acid transporter FAT/CD36 is translocated from an intracellular depot to the plasma membrane by muscle contraction (<30 min) (Bonen et al. J Biol Chem 275: 14501–14508, 2000). In the present study, we examined whether insulin also induced the translocation of FAT/CD36 in rat skeletal muscle. In studies in perfused rat hindlimb muscles, we observed that insulin increased fatty acid uptake by +51%. Insulin increased the rate of palmitate incorporation into triacylglycerols, diacylglycerols, and phospholipids ( P < 0.05) while reducing muscle palmitate oxidation ( P < 0.05). Perfusing rat hindlimb muscles with insulin increased plasma membrane FAT/CD36 by +48% ( P < 0.05), whereas concomitantly the intracellular FAT/CD36 depot was reduced by 68% ( P < 0.05). These insulin-induced effects on FAT/CD36 translocation were inhibited by the phosphatidylinositol 3-kinase inhibitor LY-294002. Thus these studies have shown for the first time that insulin can induce the translocation of FAT/CD36 from an intracellular depot to the plasma membrane.This reveals a previously unknown level of regulation of fatty acid transport by insulin and may well have important consequences in furthering our understanding of the relation between fatty acid metabolism and insulin resistance.
Acute hyperglycemia alters the ability of the normal β-cell to sense and respond to glucose
Authors: Meyer Jürgen , Sturis Jeppe , Katschinski Martin , Arnold Rudolf , Göke Burkhard , Byrne Maria M.
Published: February 2015

Impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) are associated with an impaired ability of the β-cell to sense and respond to small changes in plasma glucose. The aim of this study was to establish whether acute hyperglycemia per se plays a role in inducing this defect in β-cell response. Seven healthy volunteers with no family history of NIDDM were studied on two occasions during a 12-h oscillatory glucose infusion with a periodicity of 144 min. Once, low-dose glucose was infused at a mean rate of 6 mg · kg−1 · min−1 and amplitude 33% above and below the mean rate, and, once, high-dose glucose was infused at 12 mg · kg−1 · min−1 and amplitude 16% above and below the mean rate. Mean glucose levels were significantly higher during the high-dose compared with the low-dose glucose infusion [9.5 ± 0.8 vs. 6.8 ± 0.2 mM ( P < 0.01)], resulting in increased mean insulin secretion rates [ISRs; 469.1 ± 43.8 vs. 268.4 ± 29 pmol/min ( P < 0.001)] and mean insulin levels [213.6 ± 46 vs. 67.9 ± 10.9 pmol/l ( P < 0.008)]. Spectral analysis evaluates the regularity of oscillations in glucose, insulin secretion, and insulin at a predetermined frequency. Spectral power for glucose, ISR, and insulin was reduced during the high-dose glucose infusion [11.8 ± 1.4 to 7.0 ± 1.6 ( P < 0.02), 7.6 ± 1.5 to 3.2 ± 0.5 ( P < 0.04), and 10.5 ± 1.6 to 4.6 ± 0.7 ( P < 0.01), respectively]. In conclusion, short-term infusion of high-dose glucose to obtain glucose levels similar to those previously seen in IGT subjects results in reduced spectral power for glucose, ISR, and insulin. The reduction in spectral power previously observed for ISR in IGT or NIDDM subjects may be due partly to hyperglycemia.
MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure
Authors: Schoelch Corinna , Hübschle Thomas , Schmidt Ingrid , Nuesslein-Hildesheim Barbara
Published: February 2015

Suckling-age rats display endogenous circadian rhythmicity of metabolic rate (MR) with energy-saving, torpor-like decreases, which are sympathetically controlled and suppressed by leptin treatment. We investigated whether neonatal monosodium glutamate (MSG) treatment, known to cause arcuate nucleus damage and adult-age obesity, alters energy balance in the first two postnatal weeks. Continuously recorded MR and core temperatures (Tc) show that MSG treatment disinhibits the periodic, sympathetically controlled, energy-saving drops of Tc and MR. Increased energy expenditure thus explains reduced body fat at normal lean body mass found in MSG-treated pups artificially nourished identically to controls. In MSG-treated mother-reared pups, lean body mass is additionally reduced, suggesting that MSG also reduces suckling. Plasma leptin levels are similar in controls and MSG-treated pups but higher per unit of fat mass in the latter. We conclude that the postweaning development of MSG obesity and depressed thermogenesis are preceded by an early phase of increased energy expenditure with decreased fat deposition during suckling age and hypothesize cell damage in the arcuate nucleus to be involved in both.
Shedding of TNF-α receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus
Authors: Fernandez-Real José-Manuel , Lainez Begoña , Vendrell Joan , Rigla Mercedes , Castro Antoni , Peñarroja Georgina , Broch Montserrat , Pérez Antonio , Richart Cristobal , Engel Pablo , Ricart Wifredo
Published: February 2015

Tumor necrosis factor-α (TNF-α) is increasingly recognized as a key component in the development of insulin resistance and increased blood pressure. In a sample of 368 individuals, the ratio of soluble TNF-α receptors (sTNFR2/sTNFR1) correlated positively with systolic and diastolic blood pressure ( P < 0.01). This ratio was significantly greater in type 2 diabetic subjects (DM-2) than in type 1 diabetic patients and was greater than in control nondiabetic subjects ( P < 0.00001). The TNF-α receptor 1 (TNFR1) density in peripheral blood monocytes was similar in DM-2 patients and in nondiabetic subjects. After phorbol 12-myristate 13-acetate, TNFR1 shedding was significantly decreased in DM-2 compared with control subjects, and it was directly associated with insulin sensitivity ( r = 0.54, P = 0.03). Serum sTNFR1 concentration was also linked to the vasodilatory response to glyceryltrinitrate ( P = 0.01). Conversely, TNF-α receptor 2 shedding was negatively associated with insulin sensitivity ( r = −0.54, P = 0.03), whereas shedding of L-selectin showed no significant association. After exercise-induced lowering of blood pressure, a parallel decrease in sTNFR2/sTNFR1 was observed in DM-2 patients. Our findings suggest that insulin resistance and blood pressure are linked to altered shedding of TNF-α receptors in DM-2. The latter seems reversible and is not genetically determined.
Decreased insulin action in skeletal muscle from patients with McArdle's disease
Authors: Nielsen Jakob N. , Vissing John , Wojtaszewski Jørgen F. P. , Haller Ronald G. , Begum Najma , Richter Erik A.
Published: February 2015

Insulin action is decreased by high muscle glycogen concentrations in skeletal muscle. Patients with McArdle's disease have chronic high muscle glycogen levels and might therefore be at risk of developing insulin resistance. In this study, six patients with McArdle's disease and six matched control subjects were subjected to an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp. The muscle glycogen concentration was 103 ± 45% higher in McArdle patients than in controls. Four of six McArdle patients, but none of the controls, had impaired glucose tolerance. The insulin-stimulated glucose utilization and the insulin-stimulated increase in glycogen synthase activity during the clamp were significantly lower in the patients than in controls (51.3 ± 6.0 vs. 72.6 ± 13.1 μmol · min−1 · kg lean body mass−1, P < 0.05, and 53 ± 15 vs. 79 ± 9%, P < 0.05, n = 6, respectively). The difference in insulin-stimulated glycogen synthase activity between the pairs was significantly correlated ( r = 0.96, P < 0.002) with the difference in muscle glycogen level. The insulin-stimulated increase in Akt phosphorylation was smaller in the McArdle patients than in controls (45 ± 13 vs. 76 ± 13%, P < 0.05, respectively), whereas basal and insulin-stimulated glycogen synthase kinase 3α and protein phosphatase-1 activities were similar in the two groups. Furthermore, the ability of insulin to decrease and increase fat and carbohydrate oxidation, respectively, was blunted in the patients. In conclusion, these data show that patients with McArdle's glycogen storage disease are insulin resistant in terms of glucose uptake, glycogen synthase activation, and alterations in fuel oxidation. The data further suggest that skeletal muscle glycogen levels play an important role in the regulation of insulin-stimulated glycogen synthase activity.
Temporal gradients in shear stimulate osteoblastic proliferation via ERK1/2 and retinoblastoma protein
Authors: Jiang Guang-Liang , White Charles R. , Stevens Hazel Y. , Frangos John A.
Published: February 2015

Bone cells are subject to interstitial fluid flow (IFF) driven by venous pressure and mechanical loading. Rapid dynamic changes in mechanical loading cause transient gradients in IFF. The effects of pulsatile flow (temporal gradients in fluid shear) on rat UMR106 cells and rat primary osteoblastic cells were studied. Pulsatile flow induced a 95% increase in S-phase UMR106 cells compared with static controls. In contrast, ramped steady flow stimulated only a 3% increase. Similar patterns of S-phase induction were also observed in rat primary osteoblastic cells. Pulsatile flow significantly increased relative UMR106 cell number by 37 and 62% at 1.5 and 24 h, respectively. Pulsatile flow also significantly increased extracellular signal-regulated kinase (ERK1/2) phosphorylation by 418%, whereas ramped steady flow reduced ERK1/2 activation to 17% of control. Correspondingly, retinoblastoma protein was significantly phosphorylated by pulsatile fluid flow. Inhibition of mitogen-activated protein (MAP)/ERK kinase (MEK)1/2 by U0126 (a specific MEK1/2 inhibitor) reduced shear-induced ERK1/2 phosphorylation and cell proliferation. These findings suggest that temporal gradients in fluid shear stress are potent stimuli of bone cell proliferation.
Hypothalamic thyrotropin-releasing hormone mRNA responses to hypothyroxinemia induced by sleep deprivation
Authors: Everson Carol A. , Nowak Thaddeus S.
Published: February 2015

Sleep deprivation in rats results in progressive declines in circulating concentrations of both total and free thyroxine (T4) and triiodothyronine (T3) without an expected increase in plasma thyroid-stimulating hormone (TSH). Administration of thyrotropin-releasing hormone (TRH) results in appropriate increases in plasma TSH, free T4, and free T3across experimental days, suggesting deficient endogenous TRH production and/or release. This study examined transcriptional responses related to TRH regulation following sleep deprivation. In situ hybridization was used to detect and quantitate expression of mRNAs encoding prepro-TRH and 5′-deiodinase type II (5′-DII) in brain sections of six rats sleep deprived for 16–21 days, when there was marked hypothyroxinemia, and in sections from animals yoked to the experimental protocol as well as from sham controls. TRH transcript levels in the paraventricular nucleus (PVN) were essentially unchanged at 15–16 days but increased to about threefold control levels in three of four rats sleep deprived for 20–21 days, a change comparable to that typically found in prolonged experimental hypothyroidism. There was no evidence for suppression of 5′-DII mRNA levels, which would be a sign of T3feedback downregulation of neurons in the PVN. A failure to increase serum TSH in response to hypothyroxinemia and to increased prepro-TRH mRNA expression indicates that alterations in posttranscriptional stages of TRH synthesis, processing, or release likely mediate the central hypothyroidism induced by sleep deprivation.
Redox signaling and splicing dependent change in myosin phosphatase underlie early versus late changes in NO vasodilator reserve in a mouse LPS model of sepsis
Authors: Reho John J. , Zheng Xiaoxu , Asico Laureano D. , Fisher Steven A.
Published: February 2015

Microcirculatory dysfunction may cause tissue malperfusion and progression to organ failure in the later stages of sepsis, but the role of smooth muscle contractile dysfunction is uncertain. Mice were given intraperitoneal LPS, and mesenteric arteries were harvested at 6-h intervals for analyses of gene expression and contractile function by wire myography. Contractile (myosin and actin) and regulatory [myosin light chain kinase and phosphatase subunits (Mypt1, CPI-17)] mRNAs and proteins were decreased in mesenteric arteries at 24 h concordant with reduced force generation to depolarization, Ca2+, and phenylephrine. Vasodilator sensitivity to DEA/nitric oxide (NO) and cGMP under Ca2+ clamp were increased at 24 h after LPS concordant with a switch to Mypt1 exon 24− splice variant coding for a leucine zipper (LZ) motif required for PKG-1α activation of myosin phosphatase. This was reproduced by smooth muscle-specific deletion of Mypt1 exon 24, causing a shift to the Mypt1 LZ+ isoform. These mice had significantly lower resting blood pressure than control mice but similar hypotensive responses to LPS. The vasodilator sensitivity of wild-type mice to DEA/NO, but not cGMP, was increased at 6 h after LPS. This was abrogated in mice with a redox dead version of PKG-1α (Cys42Ser). Enhanced vasorelaxation in early endotoxemia is mediated by redox signaling through PKG-1α but in later endotoxemia by myosin phosphatase isoform shifts enhancing sensitivity to NO/cGMP as well as smooth muscle atrophy. Muscle atrophy and modulation may be a novel target to suppress microcirculatory dysfunction; however, inactivation of inducible NO synthase, treatment with the IL-1 antagonist IL-1ra, or early activation of α-adrenergic signaling did not suppressed this response.
Acute Hepatocellular Drug Induced Liver Injury Probably by Alfuzosin
Authors: Cicek Tufan , Gokturk Huseyin Savas , Unler Gulhan Kanat
Published: February 2015

Alpha blockers are the drugs that exert their effects by binding to alpha receptors and relaxing smooth muscles and are currently used for treatment of benign prostate hyperplasia (BPH). These drugs are often tolerated well by the patients. However, they also possess some common side effects. Hepatotoxicity, on the other hand, is quite rare. We report herein a case with the rare complication of acute hepatocellular drug induced liver injury (DILI) by administration of Alfuzosin.
Neural Network Control for the Probe Landing Based on Proportional Integral Observer
Authors: Li Yuanchun , Ma Tianhao , Zhao Bo
Published: February 2015

For the probe descending and landing safely, a neural network control method based on proportional integral observer (PIO) is proposed. First, the dynamics equation of the probe under the landing site coordinate system is deduced and the nominal trajectory meeting the constraints in advance on three axes is preplanned. Then the PIO designed by using LMI technique is employed in the control law to compensate the effect of the disturbance. At last, the neural network control algorithm is used to guarantee the double zero control of the probe and ensure the probe can land safely. An illustrative design example is employed to demonstrate the effectiveness of the proposed control approach.
Resistance to Cotrimoxazole and Other Antimicrobials among Isolates from HIV/AIDS and Non-HIV/AIDS Patients at Bugando Medical Centre, Mwanza, Tanzania
Authors: Marwa Karol J. , Mushi Martha F. , Konje Eveline , Alele Paul E. , Kidola Jeremiah , Mirambo Mariam M.
Published: February 2015

Bacterial resistance has increased in the AIDS era and is attributed to the widespread use of cotrimoxazole prophylaxis against opportunistic infections in HIV/AIDS patients. In Tanzania, cotrimoxazole prophylaxis has been used for more than ten years. Little is known, however, about its impact on the spread of antibiotic resistance in HIV positive patients. This cross-sectional study was done to compare magnitude of bacterial resistance to cotrimoxazole and other antimicrobials among isolates from HIV infected patients on cotrimoxazole prophylaxis and those not on prophylaxis and non-HIV patients attending Bugando Medical Centre (BMC). Susceptibility testing on obtained urine and swab specimens followed Clinical Laboratory Standard Institute, 2010, Guidelines. Of 945 samples collected, 155 had positive bacterial growth after 24 hours of incubation. Of the positive samples (72), 46.4% were from HIV positive patients. The common isolates wereE. coli41.3% (64/155),Klebsiella pneumoniae17.5% (27/155), andStaphylococcus aureus16.1% (25/155). Overall, bacterial resistance to cotrimoxazole was 118 (76.1%); among isolates from HIV patients bacterial resistance was 54 (75%), and for isolates from HIV patients on prophylaxis bacterial resistance was 36 (81.3%). HIV seropositivity and cotrimoxazole prophylaxis are not associated with antibiotic resistance observed in bacteria infecting patients attending BMC, Mwanza, Tanzania.
Lactic Acid Bacteria Strains Exert Immunostimulatory Effect onH. pylori-Induced Dendritic Cells
Authors: Wiese Małgorzata , Eljaszewicz Andrzej , Helmin-Basa Anna , Andryszczyk Marek , Motyl Ilona , Wieczyńska Jolanta , Gackowska Lidia , Kubiszewska Izabela , Januszewska Milena , Michałkiewicz Jacek
Published: February 2015

The aim of this study was to find out if selected lactic acid bacteria (LAB) strains (antagonistic or nonantagonistic againstH. pylori in vitro) would differ in their abilities to modulate the DCs maturation profiles reflected by their phenotype and cytokine expression patterns.Methods. Monocyte-derived DCs maturation was elicited by their direct exposure to the LAB strains ofL. rhamnosus900 orL. paracasei915 (antagonistic and nonantagonistic toH. pylori, resp.), in the presence or absence ofH. pyloristraincagA+. The DCs maturation profile was assessed on the basis of surface markers expression and cytokines production.Results. We observed that the LAB strains and the mixtures of LAB withH. pyloriare able to induce mature DCs. At the same time, theL. paracasei915 leads to high IL-10/IL-12p70 cytokine ratio, in contrast toL. rhamnosus900.Conclusions. This study showed that the analyzed lactobacilli strains are more potent stimulators of DC maturation thanH. pylori. Interestingly from the two chosen LAB strains the antagonistic toH. pylori-L. rhamnosusstrain 900 has more proinflammatory and probably antibactericidal properties.
A Bayesian Method for Water Resources Vulnerability Assessment: A Case Study of the Zhangjiakou Region, North China
Authors: Wang Xuan , Ma Fangbing , Li Chunhui , Zhu Jie
Published: February 2015

Water resources vulnerability (WRV) assessment is an important basis for maintaining water resources security in a basin. In this paper, considering the complexity of the water resources system and the uncertainty of the assessment information, a method based on the Bayesian theory was developed for performing WRV assessments while using the constructed indicator system. This system includes four subsystems, the hydrological subsystem, the socioeconomic subsystem, the ecoenvironmental subsystem and the hydraulic engineering subsystem. The WRV degree for each subsystem and the integrated water resources system were assessed. Finally, the assessment results and the characteristics of the Bayesian method were compared with those of the grey relational analysis method and the parametric-system method. The results showed the following. (1) The WRV of the integrated water resources system of the entire Zhangjiakou region was very high; Zhangjiakou City and Xuanhua County have tendencies to belong to Extreme WRV, with probabilities of 26.8% and 25%, respectively, while the other seven administrative counties have tendencies to belong to High WRV, with probabilities ranging from 24.6% to 27%. (2) Compared with the parametric-system method and the grey relational analysis method, the Bayesian method is simple and can effectively address the uncertainty issues with the reliable WRV assessment results.
Modeling the Relationship between Vibration Features and Condition Parameters Using Relevance Vector Machines for Health Monitoring of Rolling Element Bearings under Varying Operation Conditions
Authors: Hu Lei , Hu Niao-qing , Fan Bin , Gu Feng-shou , Zhang Xiang-yi
Published: February 2015

Rotational speed and load usually change when rotating machinery works. Both this kind of changing operational conditions and machine fault could make the mechanical vibration characteristics change. Therefore, effective health monitoring method for rotating machinery must be able to adjust during the change of operational conditions. This paper presents an adaptive threshold model for the health monitoring of bearings under changing operational conditions. Relevance vector machines (RVMs) are used for regression of the relationships between the adaptive parameters of the threshold model and the statistical characteristics of vibration features. The adaptive threshold model is constructed based on these relationships. The health status of bearings can be indicated via detecting whether vibration features exceed the adaptive threshold. This method is validated on bearings running at changing speeds. The monitoring results show that this method is effective as long as the rotational speed is higher than a relative small value.
Prevalence of Human Papillomavirus Variants and Genetic Diversity in the L1 Gene and Long Control Region of HPV16, HPV31, and HPV58 Found in North-East Brazil
Authors: Gurgel Ana Pavla Almeida Diniz , Chagas Bárbara Simas , do Amaral Carolina Medeiros , Nascimento Kamylla Conceição Gomes , Leal Lígia Rosa Sales , Silva Neto Jacinto da Costa , Cartaxo Muniz Maria Tereza , de Freitas Antonio Carlos
Published: February 2015

This study showed the prevalence of human papillomavirus (HPV) variants as well as nucleotide changes within L1 gene and LCR of the HPV16, HPV31, and HPV58 found in cervical lesions of women from North-East Brazil.