Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through the GLUT4 glucose transporter ...which translocates from intracellular storage depots to the plasma membrane and T-tubules upon muscle contraction. Here we discuss the current understanding of how exercise-induced muscle glucose uptake is regulated. We briefly discuss the role of glucose supply and metabolism and concentrate on GLUT4 translocation and the molecular signaling that sets this in motion during muscle contractions. Contraction-induced molecular signaling is complex and involves a variety of signaling molecules including AMPK, Ca(2+), and NOS in the proximal part of the signaling cascade as well as GTPases, Rab, and SNARE proteins and cytoskeletal components in the distal part. While acute regulation of muscle glucose uptake relies on GLUT4 translocation, glucose uptake also depends on muscle GLUT4 expression which is increased following exercise. AMPK and CaMKII are key signaling kinases that appear to regulate GLUT4 expression via the HDAC4/5-MEF2 axis and MEF2-GEF interactions resulting in nuclear export of HDAC4/5 in turn leading to histone hyperacetylation on the GLUT4 promoter and increased GLUT4 transcription. Exercise training is the most potent stimulus to increase skeletal muscle GLUT4 expression, an effect that may partly contribute to improved insulin action and glucose disposal and enhanced muscle glycogen storage following exercise training in health and disease.
As the principal tissue for insulin-stimulated glucose disposal, skeletal muscle is a primary driver of whole-body glycemic control. Skeletal muscle also uniquely responds to muscle contraction or ...exercise with increased sensitivity to subsequent insulin stimulation. Insulin's dominating control of glucose metabolism is orchestrated by complex and highly regulated signaling cascades that elicit diverse and unique effects on skeletal muscle. We discuss the discoveries that have led to our current understanding of how insulin promotes glucose uptake in muscle. We also touch upon insulin access to muscle, and insulin signaling toward glycogen, lipid, and protein metabolism. We draw from human and rodent studies in vivo, isolated muscle preparations, and muscle cell cultures to home in on the molecular, biophysical, and structural elements mediating these responses. Finally, we offer some perspective on molecular defects that potentially underlie the failure of muscle to take up glucose efficiently during obesity and type 2 diabetes.
Variations in the Arctic central Canada Basin mixed layer properties are documented based on a subset of nearly 6500 temperature and salinity profiles acquired by Ice‐Tethered Profilers during the ...period summer 2004 to summer 2009 and analyzed in conjunction with sea ice observations from ice mass balance buoys and atmosphere‐ocean heat flux estimates. The July–August mean mixed layer depth based on the Ice‐Tethered Profiler data averaged 16 m (an overestimate due to the Ice‐Tethered Profiler sampling characteristics and present analysis procedures), while the average winter mixed layer depth was only 24 m, with individual observations rarely exceeding 40 m. Guidance interpreting the observations is provided by a 1‐D ocean mixed layer model. The analysis focuses attention on the very strong density stratification at the base of the mixed layer in the Canada Basin that greatly impedes surface layer deepening and thus limits the flux of deep ocean heat to the surface that could influence sea ice growth/decay. The observations additionally suggest that efficient lateral mixed layer restratification processes are active in the Arctic, also impeding mixed layer deepening.
Skeletal muscle extracts glucose from the blood to maintain demand for carbohydrates as an energy source during exercise. Such uptake involves complex molecular signalling processes that are distinct ...from those activated by insulin. Exercise-stimulated glucose uptake is preserved in insulin-resistant muscle, emphasizing exercise as a therapeutic cornerstone among patients with metabolic diseases such as diabetes mellitus. Exercise increases uptake of glucose by up to 50-fold through the simultaneous stimulation of three key steps: delivery, transport across the muscle membrane and intracellular flux through metabolic processes (glycolysis and glucose oxidation). The available data suggest that no single signal transduction pathway can fully account for the regulation of any of these key steps, owing to redundancy in the signalling pathways that mediate glucose uptake to ensure maintenance of muscle energy supply during physical activity. Here, we review the molecular mechanisms that regulate the movement of glucose from the capillary bed into the muscle cell and discuss what is known about their integrated regulation during exercise. Novel developments within the field of mass spectrometry-based proteomics indicate that the known regulators of glucose uptake are only the tip of the iceberg. Consequently, many exciting discoveries clearly lie ahead.
Organic Bioelectronics Berggren, M.; Richter-Dahlfors, A.
Advanced materials (Weinheim),
10/2007, Letnik:
19, Številka:
20
Journal Article
Recenzirano
During the last two decades, organic electroactive materials have been explored as the working material in a vast array of electronic devices, promising low‐cost, flexible, and easily manufactured ...systems. The same materials also possess features that make them unique in bioelectronics applications, where electronic signals are translated into biosignals and vice versa. Here we review, in the broadest sense, the field of organic bioelectronics, describing the electronic properties and mechanisms of the organic electronic materials that are utilized in specific biological experiments.
Bioelectronics is a technology platform that enables signal transduction between biology and traditional electronics. This technology becomes successful only if electronic signals can be translated into biological equivalences, and vice versa, at proper temporal and spatial resolution. In addition, bioelectronic devices must exhibit proper biocompatibility and biostability to function properly over time. Organic electronic devices enable several advantages as compared to inorganic electronics, in many respects, and recent progress in organic bioelectronics is described in this Review.
The interaction between insulin and exercise is an example of balancing and modifying the effects of two opposing metabolic regulatory forces under varying conditions. While insulin is secreted after ...food intake and is the primary hormone increasing glucose storage as glycogen and fatty acid storage as triglycerides, exercise is a condition where fuel stores need to be mobilized and oxidized. Thus, during physical activity the fuel storage effects of insulin need to be suppressed. This is done primarily by inhibiting insulin secretion during exercise as well as activating local and systemic fuel mobilizing processes. In contrast, following exercise there is a need for refilling the fuel depots mobilized during exercise, particularly the glycogen stores in muscle. This process is facilitated by an increase in insulin sensitivity of the muscles previously engaged in physical activity which directs glucose to glycogen resynthesis. In physically trained individuals, insulin sensitivity is also higher than in untrained individuals due to adaptations in the vasculature, skeletal muscle and adipose tissue. In this paper, we review the interactions between insulin and exercise during and after exercise, as well as the effects of regular exercise training on insulin action.
AMPK (AMP-activated protein kinase) is a phylogenetically conserved fuel-sensing enzyme that is present in all mammalian cells. During exercise, it is activated in skeletal muscle in humans, and at ...least in rodents, also in adipose tissue, liver and perhaps other organs by events that increase the AMP/ATP ratio. When activated, AMPK stimulates energy-generating processes such as glucose uptake and fatty acid oxidation and decreases energy-consuming processes such as protein and lipid synthesis. Exercise is perhaps the most powerful physiological activator of AMPK and a unique model for studying its many physiological roles. In addition, it improves the metabolic status of rodents with a metabolic syndrome phenotype, as does treatment with AMPK-activating agents; it is therefore tempting to attribute the therapeutic benefits of regular physical activity to activation of AMPK. Here we review the acute and chronic effects of exercise on AMPK activity in skeletal muscle and other tissues. We also discuss the potential role of AMPK activation in mediating the prevention and treatment by exercise of specific disorders associated with the metabolic syndrome, including Type 2 diabetes and Alzheimer's disease.
Tropospheric NO2 , a key pollutant in particular in cities, has been measured from space since the mid-1990s by the GOME, SCIAMACHY, OMI, and GOME-2 instruments. These data provide a unique global ...long-term dataset of tropospheric pollution. However, the observations differ in spatial resolution, local time of measurement, viewing geometry, and other details. All these factors can severely impact the retrieved NO2 columns. In this study, we present three ways to account for instrumental differences in trend analyses of the NO2 columns derived from satellite measurements, while preserving the individual instruments' spatial resolutions. For combining measurements from GOME and SCIAMACHY into one consistent time series, we develop a method to explicitly account for the instruments' difference in ground pixel size (40 × 320 km2 vs. 30 × 60 km2 ). This is especially important when analysing NO2 changes over small, localised sources like, e.g. megacities. The method is based on spatial averaging of the measured earthshine spectra and extraction of a spatial pattern of the resolution effect. Furthermore, two empirical corrections, which summarise all instrumental differences by including instrument-dependent offsets in a fitted trend function, are developed. These methods are applied to data from GOME and SCIAMACHY separately, to the combined time series, and to an extended dataset comprising also GOME-2 and OMI measurements. All approaches show consistent trends of tropospheric NO2 for a selection of areas on both regional and city scales, for the first time allowing consistent trend analysis of the full time series at high spatial resolution. Compared to previous studies, the longer study period leads to significantly reduced uncertainties. We show that measured tropospheric NO2 columns have been strongly increasing over China, the Middle East, and India, with values over east-central China tripling from 1996 to 2011. All parts of the developed world, including Western Europe, the United States, and Japan, show significantly decreasing NO2 amounts in the same time period. On a megacity level, individual trends can be as large as +27.2 ± 3.9% yr-1 and +20.7 ± 1.9% yr-1 in Dhaka and Baghdad, respectively, while Los Angeles shows a very strong decrease of -6.00 ± 0.72% yr-1 . Most megacities in China, India, and the Middle East show increasing NO2 columns of +5 to 10% yr-1 , leading to a doubling to tripling within the study period.
Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers, mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose ...transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo, but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source, regulating glucose transport capacity during moderate-intensity exercise.
•We examined potential factors influencing eDNA shedding rates of two invasive fish.•We show that the amount of eDNA shed is positively related to fish biomass.•Water temperature did not affect the ...amount of eDNA shed, but feeding and diet had an effect.•Identification of PCR inhibited samples is important for eDNA monitoring programs.
Wildlife managers can more easily mitigate the effects of invasive species if action takes place before a population becomes established. Such early detection requires sensitive survey tools that can detect low numbers of individuals. Due to their high sensitivity, environmental DNA (eDNA) surveys hold promise as an early detection method for aquatic invasive species. Quantification of eDNA amounts may also provide data on species abundance and timing of an organism’s presence, allowing managers to successfully combat the spread of ecologically damaging species. To better understand the link between eDNA and an organism’s presence, it is crucial to know how eDNA is shed into the environment. Our study used quantitative PCR (qPCR) and controlled laboratory experiments to measure the amount of eDNA that two species of invasive bigheaded carps (Hypophthalmichthys nobilis and Hypophthalmichthysmolitrix) shed into the water. We first measured how much eDNA a single fish sheds and the variability of these measurements. Then, in a series of manipulative lab experiments, we studied how temperature, biomass (grams of fish), and diet affect the shedding rate of eDNA by these fish. We found that eDNA amounts exhibit a positive relationship with fish biomass, and that feeding could increase the amount of eDNA shed by ten-fold, whereas water temperature did not have an effect. Our results demonstrate that quantification of eDNA may be useful for predicting carp density, as well as densities of other rare or invasive species.
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