S suppressed (instead of increased) in response to insulin, while subject 22 exhibited no JW-74 web insulin induction of PKB phosphorylation or IRS1 protein (despite strong induction of p42/p44 MAPK phosphorylation and activity). It is not immediately obvious why different signalling defects should arise in a relatively healthy obese population, however it may be related to dietary variations with different compositions of fatty acids altering signalling in different ways [27], or other lifestyle factors not apparent 25033180 in our study. This aspect, as well as establishingSkeletal Muscle Signalling Defects in ObesityFigure 6. Representative Western blots. Body mass indices (BMI) are shown in parentheses and effects of fasting (2) or insulin (+). doi:10.1371/journal.pone.0056928.gwhether one signalling defect is more liable to promote diabetes, deserves further investigation. In summary, aberrant p42/p44 MAPK signalling was the most common problem found in obesity-induced insulin resistant skeletal muscle. However, multiple defects in insulin signal transduction were apparent in this group and it will be of interestto establish whether the p42/p44 MAPK defect is associated with progression to T2DM.AcknowledgmentsWe would like to thank the 76932-56-4 site volunteers for participating in the study and Mrs Pat Mole for assistance in undertaking body composition analysis.Skeletal Muscle Signalling Defects in ObesityAuthor ContributionsConceived and designed the experiments: ARA MM JP DC AM CS. Performed the experiments: ARA CL JP MM CS DC. Analyzed the data:ARA CL JP MM AM CS. Contributed reagents/materials/analysis tools: ARA JP MM CS. Wrote the paper: ARA CL JP CS DC.
The pivotal role of inflammatory mechanisms in the progression of atherosclerosis has fuelled research aimed at whether diseases characterized by chronic inflammation, including inflammatory bowel disease (IBD), carry an increased risk of cardiovascular disease [1,2]. Indeed, an increased incidence of MI and stroke has been demonstrated in patients with rheumatoid arthritis, psoriasis, and systemic lupus erythematosus [3?]._ENREF_3 In patients with IBD, however, studies on the risk of atherothrombotic disease are less conclusive [6?]. Despite these inconclusive findings, it iswell-established that patients with IBD have increased risk of developing venous thromboembolic events, and recent evidence has shown that this risk is particularly elevated during periods of increased disease activity [10,11]. These findings are consistent with studies linking active inflammation to a general prothrombotic state [12?4]. IBD including the two main entities ulcerative colitis (UC) and Crohn’s disease (CD) has an estimated prevalence of 2.2 million persons in Europe alone, and linkage between IBD and atherothrombotic disease could potentially have a major impact on the management of these patients [15]. We therefore investigated the risk of MI, stroke, and cardiovascular death inActive IBD and Risk of Atherothrombotic Diseasepatients with IBD with correlation to disease activity in a nationwide Danish cohort.diagnosis of both UC and CD were identified as having unclassified IBD.Methods Data sourcesThe study was conducted and reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) recommendations [16]._ENREF_15 Each resident in Denmark is given a unique and permanent personal civil registration number at birth or immigration, which enables linkage on individual level ac.S suppressed (instead of increased) in response to insulin, while subject 22 exhibited no insulin induction of PKB phosphorylation or IRS1 protein (despite strong induction of p42/p44 MAPK phosphorylation and activity). It is not immediately obvious why different signalling defects should arise in a relatively healthy obese population, however it may be related to dietary variations with different compositions of fatty acids altering signalling in different ways [27], or other lifestyle factors not apparent 25033180 in our study. This aspect, as well as establishingSkeletal Muscle Signalling Defects in ObesityFigure 6. Representative Western blots. Body mass indices (BMI) are shown in parentheses and effects of fasting (2) or insulin (+). doi:10.1371/journal.pone.0056928.gwhether one signalling defect is more liable to promote diabetes, deserves further investigation. In summary, aberrant p42/p44 MAPK signalling was the most common problem found in obesity-induced insulin resistant skeletal muscle. However, multiple defects in insulin signal transduction were apparent in this group and it will be of interestto establish whether the p42/p44 MAPK defect is associated with progression to T2DM.AcknowledgmentsWe would like to thank the volunteers for participating in the study and Mrs Pat Mole for assistance in undertaking body composition analysis.Skeletal Muscle Signalling Defects in ObesityAuthor ContributionsConceived and designed the experiments: ARA MM JP DC AM CS. Performed the experiments: ARA CL JP MM CS DC. Analyzed the data:ARA CL JP MM AM CS. Contributed reagents/materials/analysis tools: ARA JP MM CS. Wrote the paper: ARA CL JP CS DC.
The pivotal role of inflammatory mechanisms in the progression of atherosclerosis has fuelled research aimed at whether diseases characterized by chronic inflammation, including inflammatory bowel disease (IBD), carry an increased risk of cardiovascular disease [1,2]. Indeed, an increased incidence of MI and stroke has been demonstrated in patients with rheumatoid arthritis, psoriasis, and systemic lupus erythematosus [3?]._ENREF_3 In patients with IBD, however, studies on the risk of atherothrombotic disease are less conclusive [6?]. Despite these inconclusive findings, it iswell-established that patients with IBD have increased risk of developing venous thromboembolic events, and recent evidence has shown that this risk is particularly elevated during periods of increased disease activity [10,11]. These findings are consistent with studies linking active inflammation to a general prothrombotic state [12?4]. IBD including the two main entities ulcerative colitis (UC) and Crohn’s disease (CD) has an estimated prevalence of 2.2 million persons in Europe alone, and linkage between IBD and atherothrombotic disease could potentially have a major impact on the management of these patients [15]. We therefore investigated the risk of MI, stroke, and cardiovascular death inActive IBD and Risk of Atherothrombotic Diseasepatients with IBD with correlation to disease activity in a nationwide Danish cohort.diagnosis of both UC and CD were identified as having unclassified IBD.Methods Data sourcesThe study was conducted and reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) recommendations [16]._ENREF_15 Each resident in Denmark is given a unique and permanent personal civil registration number at birth or immigration, which enables linkage on individual level ac.