bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in land use and physiological transitions of a Juniperus thurifera forest: from decline to recovery
Authors: Montesinos Daniel , Fabado Javier
Published: February 2015

Forest decline is frequently associated with infection; however, infections habitually affect trees that have been previously debilitated by environmental stress. Nevertheless, the causes and physiology of noninfectious forest decline are not well known. Some Juniperus thurifera L. forests presented severe (noninfectious) declines, with defoliations over 50%. The goal of this study was to determine the causes and characterize the physiology of this noninfectious decline, and we hypothesized that it could be related to environmental stress from increasing interspecific competition resulting from land abandonment. We randomly assigned 60 trees to either a control group or one of two competition-release treatments, i.e., vegetation clearing or soil ploughing. We characterized the physiological state of the trees both before treatment application and 14 months after treatment application. The J. thurifera trees that were declining experienced significantly lower soil nutrient and water availability, which resulted in lower leaf nutrient concentrations, lower photosynthetic rates, higher water stress, and arrested growth and reproduction. We confirmed that competition release increased nutrient availability and acquisition, reduced water deficit, improved photosynthetic rates, and abruptly stopped defoliation. Competition plays an increasingly critical role in forest conservation, particularly with the reported increase in the number of species colonizing previously unfeasible habitats due to global change and the absence of traditional activities that used to buffer competition.
Cancellation of the central singularity of the Schwarzschild solution with natural mass inversion process
Authors: Petit Jean-Pierre , D'Agostini G.
Published: February 2015

We reconsider the classical Schwarzschild solution in the context of a Janus cosmological model. We show that the central singularity can be eliminated through a simple coordinate change and that the subsequent transit from one fold to the other is accompanied by mass inversion. In such scenario matter swallowed by black holes could be ejected as invisible negative mass and dispersed in space.
Infrared control of slow light in a slab doped by InGaN/GaN quantum dot nanostructure
Authors: Jafarzadeh Hossein , Sangachin Elnaz Ahmadi , Asadpour Seyyed Hossein
Published: February 2015

In this paper, we proposed a model for controlling the group velocity of the transmitted and reflected pulses in a slab medium doped by four-level quantum dot nanostructure. Here, an infrared signal field interacted by quantum dot nanostructure can affect the behavior of reflected and transmitted pulses. We show that in the presence and absence of infrared pulses, the other controllable parameters have essential roles for controlling the slow and fast light propagation through the medium. Moreover, we found that the simultaneous slow and fast light can be obtained for the transmitted and reflected pulses by infrared signal field. Our proposed model may be useful for ultrahigh density optical memories in quantum communication systems or in various fields of all-optical systems.
Facies architecture of a microbial–siliceous sponge-dominated carbonate platform: the Bajocian of Moscardón (Middle Jurassic, Spain)
Authors: Aurell M. , Bádenas B.
Published: February 2015

Extensive facies analysis of the outcrops located near Moscardón (Iberian basin, NE Spain) resulted in a precise reconstruction of the facies architecture of a Bajocian (Middle Jurassic) carbonate platform. Different types of microbialites occurred in the transitional area between the shallow and relatively deep carbonate platform domains, located above and below wave base level, respectively. The most significant volume of the micorbialites is found in the platform slope, located below wave base level, in a depth range of around 30–50 m. In the lower slope, during stages of rapid accommodation gain, the vertical aggradation of individual stratiform building blocks results in the formation of up to 25 m-thick microbial–siliceous sponge buildups. During stages of sea-level highstand the individual building blocks are dominated by lateral (down-slope) progradational accretion, resulting in flatter, lens-shaped buildups. The transition between the upper slope and the shallow platform area is characterized by microbial-encrusted intraclastic–bioclastic packstones. Microbial crust development helped to stabilize the seafloor, allowing the eventual accumulation and preservation of the sand-sized grains above wave base.
Importance of depositional texture in pore characterization of subsalt microbialite carbonates, offshore Brazil
Authors: Rezende M. F. , Pope M. C.
Published: February 2015

Microbialite carbonates (e.g. stromatolites, thrombolites, shrubs and spherulites) are sedimentary deposits highly influenced by their environmental settings such as water depth, water chemistry and relative energy. Lower Cretaceous subsalt microbialite carbonates, in the Santos Basin (Brazil), have complex pore systems produced by their growth framework, which are related to carbonate precipitation by biotic and abiotic processes and also influenced by subsequent cementation and dissolution. Complex pore systems and high spatial reservoir heterogeneity result in reservoirs having total porosity ranging from 2 to 27% and permeability from less than 0.01 milidarcys to 4.9 darcys. Differences in textural characteristics such as shrub size, sorting and packing lead to different pore systems that subsequently control the petrophysical properties. Cements and dissolution also modify these texturally controlled pore systems by respectively reducing or enhancing the pore volume and pore-throats. The shrub size is a primary control on changes in the pore size and affects the permeability, whereas the shrub sorting influences the primary porosity, and secondarily the permeability. Packing acts as a secondary control on porosity. As result, a sample with small shrubs, well-sorted and tight packing has lower permeability for the same range of porosity than a sample with the same characteristics, but larger shrubs.
COUNTING CHANNELS: A TUTORIAL GUIDE ON ION CHANNEL FLUCTUATION ANALYSIS
Authors: Alvarez Osvaldo , Gonzalez Carlos , Latorre Ramon
Published: February 2015

Ion channels open and close in a stochastic fashion, following the laws of probability. However, distinct from tossing a coin or a die, the probability of finding the channel closed or open is not a fixed number but can be modified (i.e., we can cheat) by some external stimulus, such as the voltage. Single-channel records can be obtained using the appropriate electrophysiological technique (e.g., patch clamp), and from these records the open probability and the channel conductance can be calculated. Gathering these parameters from a membrane containing many channels is not straightforward, as the macroscopic current I = iNPo, where i is the single-channel current, N the number of channels, and Po the probability of finding the channel open, cannot be split into its individual components. In this tutorial, using the probabilistic nature of ion channels, we discuss in detail how i, N, and Po max (the maximum open probability) can be obtained using fluctuation (nonstationary noise) analysis (Sigworth FJ. G Gen Physiol 307: 97–129, 1980). We also analyze the sources of possible artifacts in the determination of i and N, such as channel rundown, inadequate filtering, and limited resolution of digital data acquisition by use of a simulation computer program (available at www.cecs.cl ).
EVOLUTION OF A PARTNERSHIP TO IMPROVE K-16 SCIENCE EDUCATION
Authors: Goodman Barbara E.
Published: February 2015

This article grew out of a presentation at the 82nd Annual Meeting of the American Association for the Advancement of Science Pacific Division in Irvine, California in June 2001. The symposium “Sharing Science: Successful Scientist Expert-Teacher Practitioner Interactions” was organized by Drs. Nancy J. Pelaez and Barbara L. Gonzalez of California State University at Fullerton. Goodman’s presentation was entitled “The Team Approach to Outreach Activities for K-12 Teachers in a Large, Rural State.” This personal view report describes the development and evolution of educational outreach programs at the University of South Dakota School of Medicine (USDSM) and the support provided by the administration. The number and strength of the programs at USDSM have grown in direct proportion to the commitment that the institution has been willing to make to faculty members with interests in science education. Currently, USDSM has three Basic Science faculty members who spend significant effort working with K-12 students and teachers and who have been called upon nationally as consultants and reviewers for similar programs.
FORMATIVE ASSESSMENT IN PHYSIOLOGY TEACHING USING A WIRELESS CLASSROOM COMMUNICATION SYSTEM
Authors: Paschal Cynthia B.
Published: February 2015

Systems physiology, studied by biomedical engineers, is an analytical way to approach the homeostatic foundations of basic physiology. In many systems physiology courses, students attend lectures and are given homework and reading assignments to complete outside of class. The effectiveness of this traditional approach was compared with an approach in which a wireless classroom communication system was used to provide instant feedback on in-class learning activities and reading assignment quizzes. Homework was eliminated in this approach. The feedback system used stimulated 100% participation in class and facilitated rapid formative assessment. The results of this study indicate that learning of systems physiology concepts including physiology is at least, as if not more, effective when in-class quizzes and activities with instant feedback are used in place of traditional learning activities including homework. When results of this study are interpreted in light of possible effects of the September 11, 2001 terrorist attacks on student learning in the test group, it appears that the modified instruction may be more effective than the traditional instruction.
Teaching human cardiovascular and respiratory physiology with the station method
Authors: Goodman Barbara E. , Martin Douglas S. , Williams John L.
Published: February 2015

We have developed a station method to offer combined cardiovascular and respiratory physiology exercises all in one laboratory period during our medical physiology course. This laboratory was designed for first-year medical students in order to minimize equipment costs, maximize efficient use of both student and faculty time, and facilitate integration of basic cardiovascular concepts with those in respiratory physiology. We designed six stations for the students to evaluate: cardiovascular and respiratory responses to dynamic exercise, cold pressor reflex, postural influences and respiratory modulation of cardiovascular functions, forced expiratory maneuvers with inverted bell spirometers, forced expiratory maneuvers and maximal inspiratory maneuvers with electronic spirometers with and without obstruction, and respiratory muscle strength. Students worked in groups of two to four and were assessed by individual laboratory reports. Although we neglected to formally assess the impact on students of changes in laboratory design, students appeared to respond enthusiastically to the laboratory and prepared knowledgeable laboratory reports.
COMPELLING CLASSROOM DEMONSTRATIONS THAT LINK VISUAL SYSTEM ANATOMY, PHYSIOLOGY, AND BEHAVIOUR
Authors: O’Drobinak David M. , Woods Charles B.
Published: February 2015

One of our approaches to teaching a course in anatomy and physiology is to stress the fundamental, systems-level concepts. One successful strategy we use is to continually highlight the relationships among anatomy, physiology, and behavior. In this article, we describe a set of classroom demonstrations that stress these links while fostering critical thinking. These demonstrations, on the topic of sensory system structure and function, rely on two perceptual consequences of neural adaptation in the visual system: afterimages and aftereffects. Viewing specific visual stimuli under binocular or monocular conditions with interocular transfer permits several concepts to be observed and discussed, including neural adaptation, anatomical and functional segregation of visual system pathways, and the relationship among visual system structure, function, and perception. This article discusses how to produce and present the required visual stimuli, suggests a set of questions to stimulate critical thinking, and presents student evaluation of this activity.
Intrauterine growth restriction in rats is associated with hypertension and renal dysfunction in adulthood
Authors: Battista Marie-Claude , Oligny Luc L. , St-Louis Jean , Brochu Michèle
Published: February 2015

Epidemiological studies have produced evidence that unfavorable intrauterine environments during fetal life may lead to adverse outcomes in adulthood. We have previously shown that a low-sodium diet, given to pregnant rats over the last week of gestation, results in intrauterine growth restriction (IUGR). We hypothesize that pups born with IUGR are more susceptible to the development of hypertension in adulthood. IUGR fetuses and rats aged 1 wk were characterized for organ growth and renal morphogenesis. The adults (12 wk) were evaluated for weight, systolic blood pressure, activity of the renin-angiotensin-aldosterone system (RAAS), and renal function; hearts and kidneys underwent a histological examination. Brain and cardiac ventricle-to-body ratios were increased in IUGR fetuses compared with age-matched controls, whereas the kidney-to-body ratio was unchanged. Systolic blood pressure was elevated in both IUGR male and female adults. Plasma aldosterone levels were not correlated with increased plasma renin activity. Moreover, urinary sodium was decreased, whereas plasma urea was elevated in both males and females, and creatinine levels were augmented only in females, suggesting a glomerular filtration impairment in IUGR. In our model of IUGR induced by a low-sodium diet given to pregnant rats, high blood pressure, alteration of the RAAS, and renal dysfunction are observed in adult life. Differences observed between male and female adults suggest the importance of gender in outcomes in adulthood after IUGR.
Accelerated substrate cycling: a new energy-wasting role for leptin in vivo
Authors: Reidy Shannon P. , Weber Jean-Michel
Published: February 2015

Simultaneous lipolysis and reesterification form the triacylglycerol/fatty acid (TAG/FA) cycle, a substrate cycle commonly used for thermogenesis. Its rate was measured in vivo by indirect calorimetry and continuous infusion of [2-3H]glycerol and [1-14C]palmitate, after injection of leptin or vehicle saline in rabbits. Leptin stimulated in vivo lipolysis from 9.66 ± 0.62 to 14.78 ± 0.93 μmol · kg−1· min−1, the rate of appearance of FA from 20.69 ± 2.14 to 29.03 ± 3.03 μmol · kg−1· min−1, and TAG/FA cycling from 24.82 ± 1.73 to 37.09 ± 2.49 μmol FA · kg−1· min−1. This large increase in total cycling was caused by an 85% rise in primary cycling (reesterification without transit in the circulation) and accounted for 14% of the difference in metabolic rate between the controls and the leptin-treated animals. This study shows that leptin causes a strong activation of TAG/FA cycling, lipolysis, and FA oxidation, shifting fuel preference from carbohydrates to lipids. Therefore, the acceleration of substrate cycling is a new mechanism triggered by leptin to increase metabolic rate, besides the known induction of uncoupling proteins.
Mutations in aldosterone synthase gene of Milan hypertensive rats: phenotypic consequences
Authors: Lloyd-MacGilp Susan A. , Torielli Lucia , Bechtel Stephanie , Tripodi Grazia , Gomez-Sanchez Celso E. , Zagato Laura , Bernhardt Rita , Kenyon Christopher J.
Published: February 2015

Using in vitro and in vivo methods, we have demonstrated increased sensitivity of adrenocortical steroidogenesis to ACTH in Milan hypertensive (MHS) compared with normotensive (MNS) rats and have investigated whether this is caused by mutations of steroidogenic enzymes. Genes encoding aldosterone synthase ( CYP11B2) and 11β-hydroxylase ( CYP11B1) in MHS and MNS have been cloned and sequenced. Nucleotide 752 (G) in exon 4 of MHS CYP11B2 differs from that of MNS (A); CYP11B1sequences were identical. The nucleotide 752 mutation caused a Q251R substitution in the amino acid sequence of MHS CYP11B2..The phenotype of MHS CYP11B2alleles, when expressed in COS-1 cells, differed from that of MNS alleles. The relative activities of the three reactions catalyzed by CYP11B2 (11β-hydroxylation of deoxycorticosterone, 18-hydroxylation of corticosterone, and dehydrogenation of 18-hydroxycorticosterone) were estimated after incubation of transfected cells with [14C]deoxycorticosterone and analysis of radioactivity associated with deoxycorticosterone, corticosterone, 18 hydroxycorticosterone, and aldosterone. Both 11- and 18-hydroxylase activities were lower (19 and 12%, respectively; P < 0.01 and P < 0.05) in cells transfected with MHS compared with MNS alleles, whereas 18-oxidase activity was 42% higher ( P < 0.01). To assess the significance of the CYP11B2 mutation in vivo, DNA from F2 hybrid MHS × MNS rats was genotyped. MHS alleles were associated with lower urine volumes in both sexes, lower ventricle weights in male rats, but no difference in systolic or diastolic blood pressures between the sexes. We conclude that a mutation in CYP11B2may affect aldosterone secretion in MHS; however, under normal environmental circumstances, we were unable to demonstrate any influence of this mutation on blood pressure.
Metabolic changes in the glucose-induced apoptotic blastocyst suggest alterations in mitochondrial physiology
Authors: Chi Maggie M.-Y. , Hoehn Amanda , Moley Kelle H.
Published: February 2015

Mammalian preimplantation embryos experience a critical switch from an oxidative to a predominantly glycolytic metabolism. In this study, the change in nutrient metabolism between the 2-cell and blastocyst stages was followed by measuring single embryo concentrations of tricarboxylic acid (TCA) cycle and glycolytic metabolites with microfluorometric enzymatic cycling assays. When the normal values were established, further changes that occur as a result of the induction of apoptosis by exposure to high-glucose conditions were examined. From the 2-cell to the blastocyst stage, the embryos experienced an increase in TCA metabolites and a dramatic increase in fructose 1,6-bisphosphate (FBP). The high TCA metabolites may result from accumulation of substrate due to a slowing of TCA cycle metabolism as glycolysis predominates. Embryos exposed to elevated glucose conditions experienced significantly lower FBP, suggesting decreased glycolysis, significantly higher pyruvate, suggesting increased pyruvate uptake by the embryos in response to decreased glycolysis, and increased TCA metabolites, suggesting an inability to oxidize the pyruvate and a slowing of the TCA cycle. We speculate that the glycolytic changes lead to dysfunction of the outer mitochondrial membrane that results in the abnormal TCA metabolite pattern and triggers the apoptotic event.
Allopregnanolone enhancement of GABAergic transmission in rat medial preoptic area neurons
Authors: Uchida Soko , Noda Eiichiro , Kakazu Yasuhiro , Mizoguchi Yoshihito , Akaike Norio , Nabekura Junichi
Published: February 2015

γ-Aminobutyric acid (GABA)-mediated transmission in the medial preoptic area (MPOA) of the hypothalamus plays an important role in functions such as sex steroid hormone dynamics and control of body temperature. The action of allopregnanolone, the primary metabolite of progesterone, on GABAergic transmission was investigated by employing patch clamp whole cell recording on acutely dissociated rat MPOA neurons with the functional connection of presynaptic terminals. Allopregnanolone enhanced spontaneous GABA release on the MPOA neurons and induced prolonged decay of miniature GABAergic-inhibitory postsynaptic currents (mIPSCs). The facilitation of GABA release from the presynaptic terminals by allopregnanolone disappeared in Ca2+-free extracellular solution. The presynaptic action of this neurosteroid was also blocked by bumetanide, a blocker of cation-Cl− cotransporters, and by removal of extracellular Na+. The results suggest that allopregnanolone enhances GABAergic transmission at the MPOA neurons by pre- and postsynaptic mechanisms. The enhancement of GABA release by allopregnanolone might require a high Cl− concentration in the presynaptic terminal maintained by Na+-dependent, bumetanide-sensitive mechanisms (e.g., Na+-K+-Cl− cotransporter) and might be mediated by Ca2+ influx into presynaptic terminal.
Measurement of muscle protein fractional synthesis and breakdown rates from a pulse tracer injection
Authors: Zhang Xiao-Jun , Chinkes David L. , Wolfe Robert R.
Published: February 2015

We have developed a new method to determine the fractional synthesis rate (FSR) and breakdown rate (FBR) of muscle protein. This method involves a pulse tracer injection and measurement of enrichment in the arterial blood and muscle at three time points. The calculations of FSR and FBR are based on the precursor-product principle. To test this method, we gave a pulse injection ofl-[ ring-13C6]phenylalanine of 4–6 mg/kg in five rabbits. The measured FBR value (0.233 ± 0.060%/h) was almost identical ( P = 0.35) to that (0.217 ± 0.078%/h) estimated from a leg arteriovenous balance model (Biolo G, Chinkes D, Zhang X-J, and Wolfe RR. J Parenter Enteral Nutr 16: 305–315, 1992). The measured FSR value tended to be lower than that estimated from the leg model (0.125 ± 0.036 vs. 0.185 ± 0.086%/h; P = 0.14), possibly because the new method measures only muscle FSR, whereas the leg balance model also includes skin and bone contributions. The pulse tracer injection did not affect muscle protein kinetics as measured by leucine and phenylalanine kinetics in the leg. In another five rabbits, we demonstrated that sampling could be reduced to either one or two muscle biopsies when multiple pulse injections were used. This method can be completed in 1 h with one muscle biopsy and has technical advantages over currently used methods.
Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice
Authors: Gregoire Francine M. , Zhang Qin , Smith Steven J. , Tong Carmen , Ross David , Lopez Henry , West David B.
Published: February 2015

The effects of high-fat feeding on the development of obesity were evaluated in intercellular adhesion molecule-1 (ICAM-1) knockout and C57BL/6J (B6) male mice fed a high-fat diet for ≤50 days. Serum and tissues were collected at baseline and after 1, 11, and 50 days on the diet. After 11 days on the diet, ICAM-1-deficient, but not B6, mice developed fatty livers and showed a significant increase in inguinal fat pad weight. At day 50, ICAM-1-deficient mice weighed less, and their adiposity index and circulating leptin levels were significantly lower than those of B6 controls. To better understand the early differential response to the diet, liver gene expression was analyzed at three time points by use of Affymetrix GeneChips. In both strains, a similar pattern of gene expression was detected in response to the high-fat diet. However, sterol regulatory element-binding protein-1, apolipoprotein A4, and adipsin mRNAs were significantly induced in ICAM-1-deficient livers, suggesting that these genes and their associated pathways may be involved in the acute diet response observed in the knockout mice.
Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissue
Authors: Lynch Christopher J. , Patson Brian J. , Anthony Joshua , Vaval Alain , Jefferson Leonard S. , Vary Thomas C.
Published: February 2015

In freshly isolated rat adipocytes, leucine or its analog norleucine activates the mammalian target of rapamycin (mTOR)-signaling pathway. This results in phosphorylation of the ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), two proteins involved in the initiation phase of protein synthesis. The purpose of the studies reported herein was to address the question of whether or not these in vitro effects of leucine and norleucine on adipocytes could be extended to the intact animal and to other tissues. To accomplish this, food-deprived (18 h) male Sprague-Dawley rats were orally administered solutions (2.5 ml/100 g body wt) containing normal saline (0.9% NaCl), a carbohydrate mixture (26.2% d-glucose and 26.2% sucrose), leucine (5.4%), or norleucine (5.4%). The protein synthetic responses of adipose tissue were measured and compared with those of other tissues. In addition, S6K1 and 4E-BP1 phosphorylation was measured, as was the plasma concentration of insulin and tissue ATP concentrations. Leucine administration stimulated protein synthesis in adipose tissue, gastrocnemius, and kidney but not in liver and heart. Norleucine stimulated protein synthesis in all of the tissues tested but, in contrast to leucine, without affecting plasma insulin concentrations. The carbohydrate meal had no effect on protein synthesis in any tissue tested but elicited a robust increase in plasma insulin. These findings provide support for a role of leucine as a direct-acting nutrient signal for stimulation of protein synthesis in adipose tissue as well as other select tissues. In adipose tissue, the effects of the different treatment conditions on the acute regulation of protein synthesis closely correlated with changes in phosphorylation of S6K1 and 4E-BP1; however, this correlation did not exist in all tissues examined. This result implies that leucine or norleucine may acutely stimulate protein synthesis, at least in some tissues, by a mechanism that is independent of both S6K1 and 4E-BP1 phosphorylation.
Phosphorylated inositol compounds in β-cell stimulus-response coupling
Authors: Barker Christopher J. , Leibiger Ingo B. , Leibiger Barbara , Berggren Per-Olof
Published: February 2015

Pancreatic β-cell function is essential for the regulation of glucose homeostasis in humans, and its impairment leads to the development of type 2 diabetes. Inputs from glucose and cell surface receptors act together to initiate the β-cell stimulus-response coupling that ultimately leads to the release of insulin. Phosphorylated inositol compounds have recently emerged as key players at all levels of the stimulus-secretion coupling process. In this current review, we seek to highlight recent advances in β-cell phosphoinositide research by dividing our examination into two sections. The first involves the events that lead to insulin secretion. This includes both new roles for inositol polyphosphates, particularly inositol hexakisphosphate, and both conventional and 3-phosphorylated inositol lipids. In the second section, we deal with the more novel concept of the autocrine role of insulin. Here, released insulin initiates signal transduction cascades, principally through the activity of phosphatidylinositol 3-kinase. This new round of signal transduction has been established to activate key β-cell genes, particularly the insulin gene itself. More controversially, this insulin feedback has also been suggested to either terminate or enhance insulin secretion events.
Effect of epinephrine on glucose disposal during exercise in humans: role of muscle glycogen
Authors: Watt Matthew J. , Hargreaves Mark
Published: February 2015

This study examined the effect of epinephrine on glucose disposal during moderate exercise when glycogenolytic flux was limited by low preexercise skeletal muscle glycogen availability. Six male subjects cycled for 40 min at 59 ± 1% peak pulmonary O2uptake on two occasions, either without (CON) or with (EPI) epinephrine infusion starting after 20 min of exercise. On the day before each experimental trial, subjects completed fatiguing exercise and then maintained a low carbohydrate diet to lower muscle glycogen. Muscle samples were obtained after 20 and 40 min of exercise, and glucose kinetics were measured using [6,6-2H]glucose. Exercise increased plasma epinephrine above resting concentrations in both trials, and plasma epinephrine was higher ( P < 0.05) during the final 20 min in EPI compared with CON. Muscle glycogen levels were low after 20 min of exercise (CON, 117 ± 25; EPI, 122 ± 20 mmol/kg dry matter), and net muscle glycogen breakdown and muscle glucose 6-phosphate levels during the subsequent 20 min of exercise were unaffected by epinephrine infusion. Plasma glucose increased with epinephrine infusion (i.e., 20–40 min), and this was due to a decrease in glucose disposal (Rd) (40 min: CON, 33.8 ± 3; EPI, 20.9 ± 4.9 μmol · kg−1· min−1, P < 0.05), because the exercise-induced rise in glucose rate of appearance was similar in the trials. These results show that glucose Rdduring exercise is reduced by elevated plasma epinephrine, even when muscle glycogen availability and utilization are low. This suggests that the effect of epinephrine does not appear to be mediated by increased glucose 6-phosphate, secondary to enhanced muscle glycogenolysis, but may be linked to a direct effect of epinephrine on sarcolemmal glucose transport.
Genetic approaches to the molecular understanding of type 2 diabetes
Authors: McCarthy Mark I. , Froguel Philippe
Published: February 2015

The appreciation that individual susceptibility to type 2 diabetes (T2D) and related components of the dysmetabolic syndrome has a strong inherited component provides a coherent framework within which to develop a molecular understanding of the pathogenesis of T2D. This review focuses on the main approaches currently adopted by researchers seeking to identify the inherited basis of T2D and the present state of our knowledge. One central theme that emerges is that progress in defining the genetic basis of the common, multifactorial forms of T2D is hindered by etiological heterogeneity: T2D is likely to represent the final common pathway of diverse interacting primary disturbances. Such heterogeneity equally compromises efforts to understand the basis for T2D by use of other approaches, such as cellular biochemistry and classical physiology. Analyses that seek to ally sophisticated physiological characterization with measures of genomic variation are likely to provide powerful tools for redressing the loss of power associated with such heterogeneity.
Copper transport to mammary gland and milk during lactation in rats
Authors: Donley Stephanie A. , Ilagan Bernard J. , Rim Hisun , Linder Maria C.
Published: February 2015

The delivery of copper to mammary gland and milk and the effects of lactation were examined in rats. Traces of67Cu/64Cu(II) were injected intraperitoneally or intravenously into virgin rats or lactating rats (2–5 days postpartum), and incorporation into blood, milk, and tissues was monitored. In virgin rats, most of the isotope first entered the liver and kidney. In lactating rats, almost 60% went directly to the mammary gland. Uptake rates and copper contents of the mammary gland were 20-fold higher in lactation.67Cu/64Cu appeared in milk and milk ceruloplasmin as rapidly as in mammary tissue and when there was no67Cu/64Cu-ceruloplasmin in the maternal plasma. Plasma125I-labeled albumin entered milk much more slowly. Milk ceruloplasmin (10 mg/l) had 25% of the67Cu/64Cu. Milk copper was 3.3 mg/l. Thus lactation markedly enhances the avidity of the mammary gland for copper, diverting most of it from liver and kidney to that tissue. Also, the primary source of milk ceruloplasmin is the mammary gland and not the maternal plasma.
Physiological and pharmacological regulation of 20-kDa growth hormone
Authors: Leung Kin-Chuen , Howe Chris , Gui Lily Y.-Y. , Trout Graham , Veldhuis Johannes D. , Ho Ken K. Y.
Published: February 2015

The 20-kDa growth hormone (GH) is generated from alternative splicing of the primary transcript of full-length 22-kDa GH. We have studied the regulation of 20-kDa GH over a range of pathophysiological conditions and in response to pharmacological stimulation using isoform-specific enzyme-linked immunosorbent assays (ELISAs). Mean 24-h levels of 20- and 22-kDa GH were higher in acromegaly and lower in GH deficiency than in normal subjects, with the 20-to-22-kDa ratio not different between the three groups. In normal subjects, 20-kDa GH was secreted in a pulsatile manner throughout the day, with peaks coinciding with those of 22-kDa GH. However, the half-life of 20-kDa GH (18.7 ± 0.8 min) was significantly longer than that of 22-kDa GH (14.7 ± 0.8 min; P < 0.02). Insulin-induced hypoglycemia, androgen, and oral estrogen caused a parallel and proportionate increase in both isoforms. Octreotide suppressed 20-kDa less rapidly than 22-kDa GH in blood. Administration of recombinant 22-kDa GH in normal subjects rapidly reduced the 20-kDa GH levels. In conclusion, 20-kDa GH is cosecreted with and circulates at a constant proportion of 22-kDa GH. The 20-kDa GH level is reduced by administration of exogenous 22-kDa GH, suggesting rapid negative feedback regulation on pituitary release.
Downregulated IRS-1 and PPARγ in obese women with gestational diabetes: relationship to FFA during pregnancy
Authors: Catalano Patrick M. , Nizielski Steven E. , Shao Jianhua , Preston Larraine , Qiao Liping , Friedman Jacob E.
Published: February 2015

Gestational diabetes mellitus (GDM) is associated with elevated postprandial free fatty acids (FFA) and insulin resistance; however, little is known about the cellular mechanisms underlying insulin resistance to suppress lipolysis during gestation. We evaluated the longitudinal changes in insulin suppression of FFA before pregnancy and in early (12–14 wk) and late (34–36 wk) gestation in obese subjects with normal glucose tolerance and in obese GDM subjects. Abdominal subcutaneous adipose tissue biopsies were also obtained during cesarean delivery from normal obese pregnant (Preg-Con), GDM, and nonpregnant obese control (Non-Preg-Con) subjects during gynecological surgery. GDM subjects had higher basal plasma FFA before pregnancy ( P = 0.055). Insulin's ability to suppress FFA levels declined from early to late gestation in both GDM and Preg-Con subjects and was significantly less in GDM subjects compared with Preg-Con subjects over time ( P = 0.025). Adipose tissue insulin receptor substrate (IRS)-1 protein levels were 43% lower ( P = 0.02) and p85α subunit of phosphatidylinositol 3-kinase was twofold higher ( P = 0.03) in GDM compared with Preg-Con subjects. The levels of peroxisome proliferator-activated receptor-γ (PPARγ) mRNA and protein were lower by 38% in Preg-Con ( P = 0.006) and by 48% in GDM subjects ( P = 0.005) compared with Non-Preg controls. Lipoprotein lipase and fatty acid-binding protein-2 mRNA levels were 73 and 52% lower in GDM compared with Preg-Con subjects ( P < 0.002). Thus GDM women have decreased IRS-1, which may contribute to reduced insulin suppression of lipolysis with advancing gestation. Decreased PPARγ and its target genes may be part of the molecular mechanism to accelerate fat catabolism to meet fetal nutrient demand in late gestation.
Fibroblast growth factor receptor 4 (FGFR4) mediates signaling to the prolactin but not the FGFR4 promoter
Authors: Yu Shunjiang , Zheng Lei , Asa Sylvia L. , Ezzat Shereen
Published: February 2015

Fibroblast growth factor receptors (FGFRs) have been implicated in a multitude of activities. Signaling of the 23 members of the FGF family is mediated through FGFR1–4. We show that FGF-19, which selectively binds FGFR4, can induce prolactin (PRL) but not growth hormone expression. FGF-19 also stimulated MAPK activation, an effect that was abrogated by a soluble dominant negative (dn) form of FGFR4. The response of the pituitary PRL promoter to FGF maps to an Ets-Pit1 binding site. We have previously shown that the hematopoietic zinc finger-containing transcription factor Ikaros (Ik) regulates FGFR4 as part of an overlapping site with that for an Ets-type factor in the FGFR4 promoter. Thus, we examined whether FGF-19 might regulate its own receptor through the Ets-Ik element in the FGFR4 promoter. Ets stimulated and dn-Ets inhibited basal FGFR4 and PRL promoter activity. In contrast, Ets enhanced FGF-19-induced PRL activation but failed to confer an effect for FGF-19 on the FGFR4 promoter. We conclude that FGFR4 mediates FGF-19 signaling to the PRL promoter. Our data also suggest a possible functional role for Ik in sorting Ets signals to the FGFR4 promoter, as distinct from the PRL promoter, where Ets partners with Pit1.
Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle
Authors: Ai Hua , Ihlemann Jacob , Hellsten Ylva , Lauritzen Hans P. M. M. , Hardie D. Grahame , Galbo Henrik , Ploug Thorkil
Published: February 2015

AMP-activated protein kinase (AMPK) may mediate the stimulatory effect of contraction and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on glucose transport in skeletal muscle. In muscles with different fiber type composition from fasted rats, AICAR increased 2-deoxyglucose transport and total AMPK activity approximately twofold in epitrochlearis (EPI), less in flexor digitorum brevis, and not at all in soleus muscles. Contraction increased both transport and AMPK activity more than AICAR did. In EPI muscles, the effects of AICAR and contractions on glucose transport were partially additive despite a lower AMPK activity with AICAR compared with contraction alone. In EPI from fed rats, glucose transport responses were smaller than what was seen in fasted rats, and AICAR did not increase transport despite an increase in AMPK activity. AICAR and contraction activated both α1- and α2-isoforms of AMPK. Expression of both isoforms varied with fiber types, and α2was highly expressed in nuclei. In conclusion, AICAR-stimulated glucose transport varies with muscle fiber type and nutritional state. AMPK is unlikely to be the sole mediator of contraction-stimulated glucose transport.
Long-term high-fat feeding leads to severe insulin resistance but not diabetes in Wistar rats
Authors: Chalkley Simon M. , Hettiarachchi Manthinda , Chisholm Donald J. , Kraegen Edward W.
Published: February 2015

Although lipid excess can impair β-cell function in vitro, short-term high-fat feeding in normal rats produces insulin resistance but not hyperglycemia. This study examines the effect of long-term (10-mo) high polyunsaturated fat feeding on glucose tolerance in Wistar rats. The high fat-fed compared with the chow-fed group was 30% heavier and 60% fatter, with approximately doubled fasting hyperinsulinemia ( P < 0.001) but only marginal fasting hyperglycemia (7.5 ± 0.1 vs. 7.2 ± 0.1 mmol/l, P < 0.01). Insulin sensitivity was ∼67% lower in the high-fat group ( P < 0.01). The acute insulin response to intravenous arginine was approximately double in the insulin-resistant high-fat group ( P < 0.001), but that to intravenous glucose was similar in the two groups. After the intravenous glucose bolus, plasma glucose decline was slower in the high fat-fed group, confirming mild glucose intolerance. Therefore, despite severe insulin resistance, there was only a mildly elevated fasting glucose level and a relative deficiency in glucose-stimulated insulin secretion; this suggests that a genetic or congenital susceptibility to β-cell impairment is required for overt hyperglycemia to develop in the presence of severe insulin resistance.
Effect of the ovarian hormones on GLUT4 expression and contraction-stimulated glucose uptake
Authors: Campbell S. E. , Febbraio M. A.
Published: February 2015

This study examined the roles of the female sex steroids, 17β-estradiol (E2) and progesterone (Prog), on glucose uptake and GLUT4 protein expression. Female Sprague-Dawley rats were either sham operated (C) or ovariectomized and treated with placebo (O), E2(E), Prog (P), or both hormones at physiological doses (P + E) or the same dose of Prog with a high dose of E2(P + HiE) via timed-release pellets inserted at the time of surgery, 15 days before metabolic testing. On the morning of day 15, animals received a 300-μCi injection (ip) of 2-deoxy-[14C]glucose and then either exercised on a motorized treadmill for 30 min at 0.35 m/s or remained sedentary in their cages for the same period. Basal glucose uptake was not different between the treatment groups in either the red or white quadriceps. However, glucose uptake was decreased ( P < 0.05) in O, P, and P + E rats during exercise in the red quadriceps compared with C rats, whereas E and P + HiE treatment restored glucose uptake. Glycogen content in skeletal muscle followed similar trends, with no differences seen in resting animals. Postexercise red quadriceps glycogen levels were higher ( P < 0.05) in the E and P + HiE rats compared with O and P. Treatment of ovariectomized rats with progesterone (P rats) decreased ( P < 0.05) GLUT4 content in the red quadriceps by 21% compared with C rats. These data demonstrate that estrogen-deficient animals have a decreased ability for contraction-stimulated glucose uptake and increased glycogen use during aerobic exercise. However, changes in contraction-stimulated glucose uptake could not be explained by altered transporter protein content, since the absence of E2had no effect on GLUT4 protein.
Low-dose dexamethasone in the rat: a model to study insulin resistance
Authors: Severino C. , Brizzi P. , Solinas A. , Secchi G. , Maioli M. , Tonolo G.
Published: February 2015

The main aim of this study was to set up a new animal model to study insulin resistance. Wistar rats (6 or 7 per group) received the following for 4 wk in experiment 1: 1) vehicle, 2) 2 μg/day subcutaneous dexamethasone, 3) metformin (400 mg · kg−1· day−1os), and 4) dexamethasone plus metformin. In experiment 2the rats received the following: 1) vehicle, 2) dexamethasone, 3) dexamethasone plus arginine (2%; as substrate of the nitric oxide synthase for nitric oxide production) in tap water, and 4) dexamethasone plus isosorbide dinitrate (70 mg/kg; as direct nitric oxide donor) in tap water. Insulin sensitivity was significantly reduced by dexamethasone already at week 1, before the increase in blood pressure ( day 15) and without significant changes in body weight compared with vehicle. Dexamethasone-treated rats had significantly higher triglycerides, hematocrit, and insulin, whereas serum total nitrates/ nitrites were lower compared with vehicle. The concomitant treatment with metformin minimized all the described effects of dexamethasone. In experiment 2, only isosorbide dinitrate was able to prevent the observed dexamethasone-induced metabolic, hemodynamic, and insulin sensitivity changes. Chronic low-dose subcutaneous dexamethasone (2 μg/day) is a useful model to study the relationships between insulin resistance and blood pressure in the rat, and dexamethasone might decrease insulin sensitivity and increase blood pressure through an endothelium-mediated mechanism.
Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone
Authors: Lewis Michael I. , Horvitz Gail D. , Clemmons David R. , Fournier Mario
Published: February 2015

Recent studies suggest that the anabolic effects of testosterone in muscle may be mediated, in part, by the insulin-like growth factor (IGF) system. The aim of this study was to examine the effects of nandrolone (NAN) on both IGF-I and IGF-binding proteins (IGFBPs) in the diaphragm muscle of 1-yr-old female rats. NAN (6.6 mg · kg−1· day−1) was infused continuously for 17 days using a subcutaneous Silastic implant, whereas controls (CTL) received blank capsules. Muscle fibers were classified immunohistochemically, and fiber cross-sectional areas (CSA) were determined quantitatively. IGF-I levels in both serum and muscle were determined by RIA. Immunoreactivity to an IGF-I antibody was used to localize IGF-I expression within individual muscle fibers. Muscle IGFBPs were determined by SDS-PAGE and Western ligand blotting and measured by scanning densitometry. Body weight was higher in the NAN group compared with CTL (9.4 ± 4.5% vs. −0.6 ± 3.1%). There were no changes in the fiber composition of the diaphragm. NAN increased the CSA of type IIa (20%) and type IIx/b (30%) diaphragm fibers. Levels of IGF-I in the diaphragm muscle were significantly higher (50%) in NAN-treated animals. Immunohistochemistry revealed increased localization of IGF-I within type IIx/b diaphragm fibers. In addition, NAN increased IGFBP-3 within the diaphragm (69%), whereas IGFBP-4 decreased (40%). We conclude that NAN-induced diaphragm muscle fiber hypertrophy is mediated, in part, by influences of the IGF system within the muscle, such that coordinated changes in IGFBPs reflect a direction of change that has been associated with an anabolic response in other test systems.
Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats
Authors: Dakin Catherine L. , Small Caroline J. , Park Adrian J. , Seth Asha , Ghatei Mohammad A. , Bloom Stephen R.
Published: February 2015

Oxyntomodulin (OXM) is a product of proglucagon processing in the intestine and the central nervous system. We reported that intracerebroventricular (ICV) and intranuclear administration of OXM caused an inhibition of food intake in rats (Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, and Bloom SR. Endocrinology 142: 4244–4250, 2001). In this study, we investigated the effect of twice-daily ICV administration of OXM, 1 nmol, for 7 days. A pair-fed control was included. These animals were restricted to the food intake of the OXM group but injected twice daily with saline. OXM-treated animals gained significantly less weight than either control group ( day 8: OXM, 12.2 ± 1.9 g vs. pair fed, 21.0 ± 2.1 g; P < 0.005). OXM treatment caused a reduction in epididymal white adipose tissue (OXM, 1.13 ± 0.03 g vs. pair fed, 1.29 ± 0.04 g; P < 0.05) and interscapular brown adipose tissue (OXM, 0.15 ± 0.01 g vs. pair fed, 0.18 ± 0.01 g; P < 0.05) and increased core temperature compared with saline control, suggestive of enhanced energy expenditure. The food restriction-induced suppression in plasma TSH, seen in the pair-fed group, was prevented by OXM, potentially via increased release of hypothalamic TRH. In summary, ICV OXM causes reduced body weight gain and body adiposity following chronic administration.
Acute response of net muscle protein balance reflects 24-h balance after exercise and amino acid ingestion
Authors: Tipton Kevin D. , Borsheim Elisabet , Wolf Steven E. , Sanford Arthur P. , Wolfe Robert R.
Published: February 2015

The purpose of this study was to determine if the acute anabolic muscle response to resistance exercise and essential amino acids (EAA) reflects the response over 24 h. Seven subjects participated in the following two 24-h studies: 1) resting (REST) and 2) rest plus resistance exercise and consumption of EAA (ES). Net balance (NB) across the leg was determined for four amino acids. [13C6]phenylalanine was infused to determine mixed muscle fractional synthetic rate (FSR). Twenty-four-hour FSR was significantly greater for ES than for REST ( P = 0.003). Exchange of phenylalanine across the leg was −194 ± 74 (SE) mg for ES and −371 ± 88 mg for REST ( P = 0.07) over 24 h and 229 ± 42 mg (ES) and 28 ± 15 mg (REST; P < 0.01) over 3 h corresponding to exercise and EAA consumption for ES. The difference in phenylalanine exchange between REST and ES was not different for measurements over 24 and 3 h. Increases in NB during ES were primarily the result of increases in protein synthesis. Results for other amino acids were similar. The acute anabolic response of muscle to EAA intake and exercise is additive to the response at rest and thus reflects the 24-h response.