This research article shows that a high intensity exercise program compared to a low intensity exercise program of the same session duration and frequency, increases insulin sensitivity to a larger extend in healthy subjects. It also shows that the short insulin tolerance test can be used to detect differences in insulin sensitivity in intervention studies.
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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.
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Synthetic glucocorticoids are potent anti-inflammatory drugs but show dose-dependent metabolic side effects such as the development of insulin resistance and obesity. The precise mechanisms involved in these glucocorticoid-induced side effects, and especially the participation of adipose tissue in this are not completely understood. We used a combination of transcriptomics, antibody arrays and bioinformatics approaches to characterize prednisolone-induced alterations in gene expression and adipokine secretion, which could underlie metabolic dysfunction in 3T3-L1 adipocytes. Several pathways, including cytokine signalling, Akt signalling, and Wnt signalling were found to be regulated at multiple levels, showing that these processes are targeted by prednisolone. These results suggest that mechanisms by which prednisolone induce insulin resistance include dysregulation of wnt signalling and immune response processes. These pathways may provide interesting targets for the development of improved glucocorticoids.
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The metabolic syndrome (MetS) comprises cardiometabolic risk factors frequently found in individuals with obesity. Guidelines to prevent or reverse MetS suggest limiting fat intake, however, lowering carbohydrate intake has gained attention too. The aim for this review was to determine to what extent either weight loss, reduction in caloric intake, or changes in macronutrient intake contribute to improvement in markers of MetS in persons with obesity without cardiometabolic disease. A meta-analysis was performed across a spectrum of studies applying low-carbohydrate (LC) and low-fat (LF) diets. PubMed searches yielded 17 articles describing 12 separate intervention studies assessing changes in MetS markers of persons with obesity assigned to LC (<40% energy from carbohydrates) or LF (<30% energy from fat) diets. Both diets could lead to weight loss and improve markers of MetS. Meta-regression revealed that weight loss most efficaciously reduced fasting glucose levels independent of macronutrient intake at the end of the study. Actual carbohydrate intake and actual fat intake at the end of the study, but not the percent changes in intake of these macronutrients, improved diastolic blood pressure and circulating triglyceride levels, without an effect of weight loss. The homeostatic model assessment of insulin resistance improved with both diets, whereas high-density lipoprotein cholesterol only improved in the LC diet, both irrespective of aforementioned factors. Remarkably, changes in caloric intake did not play a primary role in altering MetS markers. Taken together, these data suggest that, beyond the general effects of the LC and LF diet categories to improve MetS markers, there are also specific roles for weight loss, LC and HF intake, but not reduced caloric intake, that improve markers of MetS irrespective of diet categorization. On the basis of the results from this meta-analysis, guidelines to prevent MetS may need to be re-evaluated.
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Eating rate is a basic determinant of appetite regulation, as people who eat more slowly feel sated earlier and eat less. Without assistance, eating rate is difficult to modify due to its automatic nature. In the current study, participants used an augmented fork that aimed to decelerate their rate of eating. A total of 114 participants were randomly assigned to the Feedback Condition (FC), in which they received vibrotactile feedback from their fork when eating too fast (i.e., taking more than one bite per 10 s), or a Non-Feedback Condition (NFC). Participants in the FC took fewer bites per minute than did those in the NFC. Participants in the FC also had a higher success ratio, indicating that they had significantly more bites outside the designated time interval of 10 s than did participants in the NFC. A slower eating rate, however, did not lead to a significant reduction in the amount of food consumed or level of satiation.These findings indicate that real-time vibrotactile feedback delivered through an augmented fork is capable of reducing eating rate, but there is no evidence from this study that this reduction in eating rate is translated into an increase in satiation or reduction in food consumption. Overall, this study shows that real-time vibrotactile feedback may be a viable tool in interventions that aim to reduce eating rate. The long-term effectiveness of this form of feedback on satiation and food consumption, however, awaits further investigation.
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Background Literature on self-management innovations has studied their characteristics and position in healthcare systems. However, less attention has been paid to factors that contribute to successful implementation. This paper aims to answer the question: which factors play a role in a successful implementation of self-management health innovations? Methods We conducted a narrative review of academic literature to explore factors related to successful implementation of self-management health innovations. We further investigated the factors in a qualitative multiple case study to analyse their role in implementation success. Data were collected from nine self-management health projects in the Netherlands. Results Nine factors were found in the literature that foster the implementation of self-management health innovations: 1) involvement of end-users, 2) involvement of local and business partners, 3) involvement of stakeholders within the larger system, 4) tailoring of the innovation, 5) utilisation of multiple disciplines, 6) feedback on effectiveness, 7) availability of a feasible business model, 8) adaption to organisational changes, and 9) anticipation of changes required in the healthcare system. In the case studies, on average six of these factors could be identified. Three projects achieved a successful implementation of a self-management health innovation, but only in one case were all factors present. Conclusions For successful implementation of self-management health innovation projects, the factors identified in the literature are neither necessary nor sufficient. Therefore, it might be insightful to study how successful implementation works instead of solely focusing on the factors that could be helpful in this process.
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