Characterising the inhibitory actions of ceramide upon insulin signaling in different skeletal muscle cell models:a mechanistic insight

International audienceCeramides are known to promote insulin resistance in a number of metabolically important tissues including skeletal muscle, the predominant site of insulin-stimulated glucose disposal. Depending on cell type, these lipid intermediates have been shown to inhibit protein kinase B (PKB/Akt), a key mediator of the metabolic actions of insulin, via two distinct pathways: one involving the action of atypical protein kinase C (aPKC) isoforms, and the second dependent on protein phosphatase-2A (PP2A). The main aim of this study was to explore the mechanisms by which ceramide inhibits PKB/Akt in three different skeletal muscle-derived cell culture models; rat L6 myotubes, mouse C2C12 myotubes and primary human skeletal muscle cells. Our findings indicate that the mechanism by which ceramide acts to repress PKB/Akt is related to the myocellular abundance of caveolin-enriched domains (CEM) present at the plasma membrane. Here, we show that ceramide-enriched-CEMs are markedly more abundant in L6 myotubes compared to C2C12 myotubes, consistent with their previously reported role in coordinating aPKC-directed repression of PKB/Akt in L6 muscle cells. In contrast, a PP2A-dependent pathway predominantly mediates ceramide-induced inhibition of PKB/Akt in C2C12 myotubes. In addition, we demonstrate for the first time that ceramide engages an aPKC-dependent pathway to suppress insulin-induced PKB/Akt activation in palmitate-treated cultured human muscle cells as well as in muscle cells from diabetic patients. Collectively, this work identifies key mechanistic differences, which may be linked to variations in plasma membrane composition, underlying the insulin-desensitising effects of ceramide in different skeletal muscle cell models that are extensively used in signal transduction and metabolic studies

Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid fatty acid composition in a muscle type specific manner in sheep.

We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α) mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole body insulin sensitivity in adult LOW sheep

Problematic Facebook use and problematic video gaming as mediators of relationship between impulsivity and life satisfaction among female and male gamers

Over the past few decades, many new technologies have emerged, such as portable computers, the internet and smartphones, which have contributed to improving the lives of individuals. While the benefits of these new technologies are overwhelmingly positive, negative consequences are experienced by a minority of individuals. One possible negative aspect of new technologies is their problematic use due to impulsive use which may lead to lower life satisfaction. The present study investigated the mediating role of problematic video gaming (PVG) and problematic Facebook use (PFU) in the relationship between impulsivity dimensions and life satisfaction as well as the relationship between impulsivity dimensions and problematic behaviors. Additionally, the potential impact of gender differences was also examined. The study comprised 673 gamers (391 females) aged 17–38 years (M = 21.25 years, SD = 2.67) selected from 1365 individuals who completed an offline survey. PFU was assessed using the Facebook Intrusion Scale, and PVG was assessed using the nine-item Internet Gaming Disorder Scale–Short-Form (IGDS9-SF). Impulsivity dimensions such as attention, cognitive instability, motor, perseverance, self-control, and cognitive complexity were assessed using the Barratt Impulsiveness Scale (BIS-11), and life satisfaction was assessed using the Satisfaction With Life Scale (SWLS). Depending on the specific impulsivity dimension, findings showed both positive and negative relationships between impulsivity and life satisfaction. Attention and perseverance subtypes of impulsivity were primarily associated with problematic behaviors. Additionally, cognitive complexity was associated with PFU among female gamers, whereas cognitive instability was associated with PVG among male gamers. Additionally, PVG was primarily associated with lower life satisfaction. However, there was no mediation effects between impulsivity dimensions and life satisfaction via PFU or PVG. These findings provide a better understanding of the relationship between problematic behaviors, life satisfaction, and impulsivity among gamers and the differences between male and female gamers

Product of Municipal Sewage Sludge Incineration as an Anthropogenic Soil

National Waste Management Plan 2014 for Poland assumes increasing the amount of municipal sewage sludge converted by thermal methods, which requires an increase in the mass of sludge thermally pretreated in cement plants, power boilers and incineration plants of sewage sludge. Before June 2010 only three municipal sewage sludge incinerators were existed in Poland, and sludge incineration accounted for only 2% of the total waste. Incineration plant of municipal sewage sludge in Lomza was launched in December 2007 as the second Polish incinerator. It uses the combustion of sewage sludge in the furnace with mechanical moving grate. A mixture of slag and ash is taken off in a moistened state and led to a landfill. The paper presents the geotechnical properties of the thermally converted municipal sewage sludge in incineration plant in Lomza to show that it can be considered as a substitute for natural soils. The research programme includes properties necessary to determine the suitability of the waste for road embankments according to Polish Standard PN-S-02205:1998. The comparison of the obtained test results and the code requirements designed for coal fly ash and bottom ash mix indicates that the product of sewage sludge combustion meets all code requirements for material suitable for road embankment. Due to the 30% reduction of CBR values after waste soaking causing relatively low CBR values of soaked waste, the product of sewage sludge incineration should be built into places isolated from ground water and precipitation. That is also indicated by the possibility of leaching of heavy metals from the waste because their content is much higher than in uncontaminated soils. For earthworks should be used guidelines applied for coal fly ash and bottom ash mix embedded in road embankments. Tested product of sewage sludge combustion in the furnace with mechanical grate are much more preferred material for earthworks than fly ash generated during incineration in a fluidised bed due to the particle size. In view of lack of data in the literature concerning the geotechnical properties of the sewage sludge incineration products, further laboratory and field studies should be conduct to confirm the usefulness of waste for earthworks

Coefficient of curvature and compaction parameters for non-cohesive soils with bimodal grain size distribution

W artykule przeprowadzono analizę wpływu uziarnienia gruntów niespoistych o nieciągłych (dwumodalnych) rozkładach uziarnienia na ich zagęszczalność. Zdolność do zagęszczania gruntów niespoistych zwykle oceniana jest na podstawie wskaźnika jednorodności uziarnienia (CU) lub łącznie na podstawie dwóch wskaźników uziarnienia − CU i wskaźnika krzywizny uziarnienia (CC). W przypadku gruntów o nieciągłych rozkładach uziarnienia wartości wskaźnika CC przeważnie są mniejsze od 0,5. Grunty te klasyfi - kowane są poza grupą gruntów dobrze zagęszczalnych – jako grunty źle uziarnione. Wyniki analiz prowadzonych z wykorzystaniem wskaźnika kształtu krzywej zagęszczalności (IC) wskazują, iż grunty o nieciągłych rozkładach uziarnienia – mimo niskich wskaźników krzywizny uziarnienia (CC) – mogą być uważane jako grunty dobrze zagęszczalne.The impact of non-cohesive soil graining with bimodal grain-size distribution on its compaction was analyzed in the paper. Ability to compaction of non-cohesive soils is usually estimated on the basis of coeffi cient of uniformity (CU) or jointly two graining coeffi cients − CU and coeffi cient of curvature (CC). In the case of soils with discontinuous grain-size distribution values of coeffi cient of curvature CC are more often lower than 0.5. Those soils are classifi ed outside the well-compacted soils, as poorly graded soils. Results of the analyses carried out with the index of compaction curve shape IC indicate that soils with discontinuous grain-size distribution – despite the low values of coeffi cient of curvature (CC) – can be considered as well-compacted soils

Influence of foundation pad width on bearing capacity and deformations of subgrade

W artykule przedstawiono sposób projektowania poduszek piaskowych jako płytkiej wymiany podłoża gruntowego. Przykłady obliczeniowe przedstawiają wpływ szerokości poduszki na nośność i osiadanie podłoża gruntowego pod ławami dwukondygnacyjnego budynku administracyjno-socjalnego, posadowionego na gruncie organicznym o miąższości 3 m. Rozważano poduszki o różnych szerokościach, określonych przez wartość kąta rozkładu naprężenia β = 0°, 30° i 45°. Stwierdzono, że konieczna jest wymiana podłoża torfowego na całej wysokości warstwy, bez względu na szerokość poduszki piaskowej. Spełnienie SGU jest możliwe jedynie przy szerokości poduszki ponad 2-krotnie większej od szerokości fundamentu.A method of designing the foundation pad as a shallow replacement of organic soil is presented in the paper. The design examples present the influence of the pad width on bearing capacity and deformations of subgrade under strip foundations of a two-storey administration building, constructed on organic ground with thickness of 3 m. The pads with different width, determined by the value of the stress distribution angle ß = 0°, 30° and 45°, were taken into consideration. It was stated that peat replacement is needed on the whole organic layer thickness, regardless of the width of the sand pad. The ultimate limit state fulfillment is possible only for the pad width over twice greater than the width of the foundation

Foundation pad reinforced by geosynthetics

W artykule omówiono wpływ zbrojenia poduszki piaskowej na nośność podłoża gruntowego i zwiększenie sztywności poduszki. Podano tok postępowania przy projektowaniu poduszki zbrojonej według zaleceń EBGEO. Obliczenia obejmują wybrane ławy dwukondygnacyjnego budynku administracyjno-socjalnego, posadowionego na gruncie organicznym o miąższości 3 m. Zaprojektowano poduszki piaskowe o różnych szerokościach określonych przez wartość kąta rozkładu naprężenia β = 0°, 30° i 45°, zbrojone czterema warstwami geosiatki. Obliczenia poduszek przeprowadzono zgodnie z wytycznymi EBGEO. Zbrojenie poduszki piaskowej ma wpływ na nośność podłoża gruntowego na wypieranie, a wpływ zbrojenia jest największy w przypadku poduszki o szerokości równej szerokości fundamentu. Wzrost sztywności poduszki, obliczony według EBGEO, wynika głównie z jej obciążenia i wytrzymałości zbrojenia na rozciąganie.The influence of the foundation pad reinforcement on bearing capacity and stiffness increasing was described in the paper. The procedure of designing the reinforced foundation pad according to EBGEO was given. The calculations for chosen strip foundation of a two-storey administration building, constructed on organic ground with thickness of 3 m, were shown. Pads with different width, determined by the value of stress distribution angle ß = 0°, 30° and 45°, reinforced by four layers of geogrid were designed based on EBGEO. Foundation pad reinforcement affects the subgrade bearing capacity, and the impact is the greatest in the case of pad with width equalled to strip foundation width. The stiffness pad increase, calculated according to EBGEO, is mainly due to pad loading and strength of the geosynthetics