Glucocorticoids (GCs), such as prednisolone (PRED), are widely prescribed anti-inflammatory drugs, but their use may induce glucose intolerance and diabetes. GC-induced beta cell dysfunction contributes to these diabetogenic effects through mechanisms that remain to be elucidated. In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to reduce the phosphorylation of PERK and its downstream substrate eIF2α. These modulations of ER stress pathways were accompanied by upregulation of calpain 10 and increased cleaved caspase 3, indicating that long term exposure to PRED ultimately promotes apoptosis. Taken together, our data suggest that the inhibition of insulin biosynthesis by PRED in the insulin-secreting INS-1E cells results, at least in part, from a GR-mediated impairment in ER homeostasis which may lead to apoptotic cell death.
Background and aimsThe aim of this study was to gain insight in the effect of a preschool-based intervention for Early Childhood Education and Care (ECEC) teachers on promoting healthy eating and physical activity in toddlers.MethodsIn a cluster randomized controlled trial, 37 preschools of child care organization Impuls in Amsterdam Nieuw-West, the Netherlands, were randomly allocated to an intervention or control group. In total, 115 female ECEC teachers (mean age 42 ± 9 years) participated. The intervention for ECEC teachers consisted of two existing Dutch programs: ‘A Healthy Start’ and ‘PLAYgrounds’. The practices and knowledge of ECEC teachers concerning healthy eating and physical activity and the level of confidence in promoting healthy eating and physical activity in toddlers was assessed at baseline and 9 months of follow-up. To examine the effect of the intervention linear mixed models were used.ResultsPreliminary analyses of the practices indicated that Activity-related-Teaching/Autonomy-Support was increased in the intervention group (mean difference: 0.181), but not in the control group (mean difference: -0.048; p-value group*time: 0.025). Food-related-Pressure-to-Eat was decreased in the intervention group (mean difference: -0.580), but not in the control group (mean difference: -0.158; p-value group*time: 0.014). No effect of the intervention was found on knowledge (p-value group*time: 0.24) and the level of confidence (p-value group*time: 0.98) of ECEC teachers. ConclusionsThe preschool-based intervention seems to increase Activity-related-Teaching/Autonomy-Support and to decrease Food-related-Pressure-to-Eat. No effects were seen on knowledge and level of confidence of ECEC teachers in promoting healthy eating and physical activity in toddlers.
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Dark homogenous fungal-based layers called biofinishes and vegetable oils are keyingredients of an innovative wood protecting system. The aim of this study was todetermine which of the vegetable oils that have been used to generate biofinishes onwood will provide carbon and energy for the biofinish-inhabiting fungus Aureobasidiummelanogenum, and to determine the effect of the oil type and the amount of oil on thecell yield. Aureobasidium melanogenum was cultivated in shake flasks with differenttypes and amounts of carbon-based nutrients. Oil-related total cell and colony-formingunit growth were demonstrated in suspensions with initially 1% raw linseed,stand linseed, and olive oil. Oil-related cell growth was also demonstrated with rawlinseed oil, using an initial amount of 0.02% and an oil addition during cultivation. Nilered staining showed the accumulation of fatty acids inside cells grown in the presenceof oil. In conclusion, each tested vegetable oil was used as carbon and energysource by A. melanogenum. The results indicated that stand linseed oil provides lesscarbon and energy than olive and raw linseed oil. This research is a fundamental stepin unraveling the effects of vegetable oils on biofinish formation.
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