Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise

We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake, glycogen synthase (GS) activity, and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic (100 microU/ml) clamp. On two occasions, seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp. Caffeine (5 mg/kg) or placebo was administered in a randomized, double-blind fashion 1 h before the clamp. During the clamp, whole-body glucose disposal was reduced (P < 0.05) in caffeine (37.5 +/- 3.1 micromol x min(-1) x kg(-1)) vs. placebo (54.1 +/- 2.9 micromol x min(-1) x kg(-1)). In accordance, the total area under the curve over 100 min (AUC(0--100 min)) for insulin-stimulated glucose uptake in caffeine was reduced (P < 0.05) by approximately 50% in rested and exercised muscle. Caffeine also reduced (P < 0.05) GS activity before and during insulin infusion in both legs. Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo. Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs. Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs. Caffeine did not alter insulin signaling in either leg. Plasma epinephrine and muscle cAMP concentrations were increased in caffeine. We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.     

Validity of the aphasia item from the Scandinavian Stroke Scale

We studied the validity of the aphasia item of a widely used stroke scale - the Scandinavian Stroke Scale (SSS) - in discriminating between aphasia and normal language function in 33 stroke patients of an acute stroke unit. They were assessed by a nurse using the aphasia item from the SSS and by a speech and language therapist carrying out a full evaluation of the language function. The latter served as the 'gold standard'. The agreement between the nurses' and the speech and language therapist's scoring was good (weighted kappa = 0.74, 95% CI 0.51-0.97), and the sensitivity and specificity of the SSS aphasia item were also satisfactory. However, the predictive value of a positive test was as low as 0.55 (95% CI 0.23-0.83), indicating nearly every second of the positives being false positive. Using the aphasia score of the SSS as a diagnostic aid for aphasia after stroke results in a high rate of false positives and inflates the prevalence figures for aphasia in epidemiological studies of stroke.     

Development and validation of an enzyme-linked immunosorbent assay to measure vitellogenin in the zebrafish (Danio rerio)

In this study, an enzyme-linked immunosorbent assay (ELISA) was developed to quantify vitellogenin (Vtg) in zebrafish (Danio rerio). Zebrafish Vtg (zf-Vtg) was purified from whole-body homogenates of estradiol-exposed zebrafish, and polyclonal antibodies against zf-Vtg were raised. Using purified zf-Vtg as a standard and anti-zf-Vtg antibodies (DR-264), a competitive ELISA method was set up and validated. The working range of the assay is from 1 to 30 ng/ml (20-80% binding), and the detection limit is 0.4 ng/ml for purified zf-Vtg. In whole-body homogenates samples, the practical detection limit is higher than that for purified Vtg (40 ng/ml) due to matrix effect. The intra- and interassay variations were 4.7% and 14%, respectively, at 50% binding (n = 36). Its usefulness to detect changes in Vtg concentration in other cyprinid fish was also tested. In addition, the assay was used to assess Vtg induction in male zebrafish exposed to 17beta-estradiol (E2). Exposure of male zebrafish to 0.1, 1, 10, and 100 microg/L of E2 for 7 d led to a Vtg induction from the lowest concentration. The results show the suitability of the developed ELISA to quantify Vtg inductions in zebrafish, the cross-reactivity of DR264 antibodies with commonly used cyprinids, and the potential of zf-Vtg induction as a sensitive biochemical endpoint that could be used to detect estrogenic properties of chemical substances.     

Acute response to precision, time pressure and mental demand during simulated computer work

OBJECTIVES: The electromyographic (EMG) activity of shoulder and forearm muscles was recorded during a standardized computer task with different combinations of time pressure, precision demands, and mental demands to study the interaction of these factors and their effect on muscular response during simulated computer work. METHODS: The computer task lasted 5 minutes, and it was performed by 14 female computer-aided design (CAD) operators during 8 exposure combinations that differed with respect to time pressure, precision demand, and mental demand. Performance (number of produced drawings, mouse clicks, and errors) were recorded. The EMG activity was recorded from the trapezius, infraspinatus, deltoid, and extensor digitorum muscles. An electrogoniometer was used to measure wrist postures and movements. RESULTS: High time pressure (combined with low precision and low mental demands) resulted in higher EMG activity for all the muscles and in a small increase in the number of produced drawings. High precision demands caused a large reduction in the number of produced drawings, but not always a change in EMG activity. High precision demands and high mental demands led to no change or a reduction in muscle activity because the number of drawings was greatly reduced. CONCLUSIONS: The interaction between work pace and other exposure factors must be taken into account when the effects of changes in exposure demands on muscular response are predicted. Only then can it be predicted whether changing demands will constitute a risk of developing musculoskeletal disorders.     

Sexual socialization and motives for intercourse among Norwegian adolescents

The impact of gender differences in sexual socialization on early sexual experiences among Norwegian adolescents is discussed. The material comprises a stratified sample of 920 adolescents ages 16–20 years in a Norwegian county. Data were collected by means of questionnaires. Of the respondents, 55.5% were girls and 44.5% were boys. 52.3% of girls and 41.4% of the boys had coital experience. The most common reasons for having had the first sexual intercourse were being in love, curiosity or excitement, and sexual arousal. Findings from a discriminant analysis showed that emotional reasons were more important to girls, whereas boys seemed more practical in sexual matters. More boys than girls reported that the reason for having had their most recent intercourse was that the partner wanted it. This indicates that if girls do not want sex, boys seldom use pressure. Girls set the premises for sexual interaction but are not as sexually skilled as boys.     

Cancer of the gastrointestinal tract and exposure to asbestos in drinking water among lighthouse keepers (Norway)

Objective Previous studies of predominantly ecological design have indicated a possible elevation of gastrointestinal cancer risk in population groups exposed to drinking water contaminated with asbestos from natural sources or asbestos–cement containing water pipes. In the present study the possible effect of ingested asbestos fibers on gastrointestinal cancer risk was investigated in an occupational group where a proportion of the employees was exposed to asbestos in their drinking water.Method A cohort of 726 lighthouse keepers first employed between 1917 and 1967 were followed up for cancer incidence from 1960 to 2002. The standardized incidence ratio (SIR) was calculated as the number of new cancer cases divided by the expected number based on five-year age and sex specific incidence rates in the general rural population of Norway. A 95% confidence interval (CI) was calculated for all SIR values assuming a Poisson distribution of the cancer cases.Results Risk of stomach cancer was elevated in the whole cohort (SIR: 1.6, CI: 1.0–2.3), in the subgroup with definite asbestos exposure (SIR: 2.5, CI: 0.9–5.5), and when the group was followed for 20 years and more after first possible exposure (SIR: 1.7, CI: 1.1–2.7). Less consistent results were found for colon cancer; SIR was 1.5 (CI: 0.9–2.2) overall, 0.8 (CI: 0.1–2.9) among the exposed, and 1.6 (CI: 1.0–2.5) twenty years and more after first possible exposure.Conclusion The results support the hypothesis of an association between ingested asbestos and gastrointestinal cancer risk in general and stomach cancer risk specifically.     

Variability in dust exposure in a cement factory in Tanzania

Dust exposure levels were studied in a cement factory in Dar es Salaam, Tanzania, as part of an epidemiological study assessing chronic respiratory health effects. One hundred and twenty personal 'total' dust samples were collected from 80 randomly selected workers from eight a priori occupational groups (OGs) based on work areas using a 37 mm Millipore sampler. The between-group, within-group and within-worker variances were determined to assess the contrast in exposure level between the OGs and to estimate the attenuation and standard error of the theoretical exposure-response slope. Using mixed-effect model estimates, the probability of overexposure relative to the occupational exposure limit (OEL) was assessed for each OG. The geometric means of total dust exposure were higher in the cranes (38.64 mg m(-3)), packing (21.30 mg m(-3)) and crusher (13.48 mg m(-3)) than in the cement mill (3.23 mg m(-3)), kiln (2.87 mg m(-3)), raw mill (1.85 mg m(-3)), maintenance (1.16 mg m(-3)) and administration (0.29 mg m(-3)). The a priori grouping scheme seems to be an efficient scheme because of the high contrast in exposure level between the OGs (0.78) and minimal attenuation of the theoretical exposure-response slope (1.0%). When using the reduced mixed-effect model, the probabilities of overexposure () relative to the OEL of 10 mg m(-3) for total cement dust were higher in the crane (96%), packing (88%) and crusher (73%) than in the cement mill (16%), kiln (14%), raw mill (5%), maintenance (2%) and administration (0.01%).     

Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation

Most lifestyle-related chronic diseases are characterized by low-grade systemic inflammation and insulin resistance. Excessive tumor necrosis factor-alpha (TNF-alpha) concentrations have been implicated in the development of insulin resistance, but direct evidence in humans is lacking. Here, we demonstrate that TNF-alpha infusion in healthy humans induces insulin resistance in skeletal muscle, without effect on endogenous glucose production, as estimated by a combined euglycemic insulin clamp and stable isotope tracer method. TNF-alpha directly impairs glucose uptake and metabolism by altering insulin signal transduction. TNF-alpha infusion increases phosphorylation of p70 S6 kinase, extracellular signal-regulated kinase-1/2, and c-Jun NH(2)-terminal kinase, concomitant with increased serine and reduced tyrosine phosphorylation of insulin receptor substrate-1. These signaling effects are associated with impaired phosphorylation of Akt substrate 160, the most proximal step identified in the canonical insulin signaling cascade regulating GLUT4 translocation and glucose uptake. Thus, excessive concentrations of TNF-alpha negatively regulate insulin signaling and whole-body glucose uptake in humans. Our results provide a molecular link between low-grade systemic inflammation and the metabolic syndrome.     

Genetic background determines the size and structure of the endocrine pancreas

Key parameters of the endocrine pancreas, such as islet number, islet mass, beta-cell mass, and alpha-cell mass, were studied in different strains of inbred mice to investigate the impact of genetic background on the size and structure of the endocrine pancreas. Six mice from each of seven different strains of inbred mice were included in the study. For all parameters investigated, there was a pronounced interstrain variation. ANCOVA showed that only mouse strain was statistically significant as an explanatory parameter for the number of islets. Mouse strain, body weight, and pancreas mass reached statistical significance as explanatory parameters for the islet mass, with mouse strain as the most significant predictor. These data show that genetic background is the most important predictor of both the number of islets and total islet volume. We also conclude that inbred mice could be a valuable resource to identify the genes responsible for the size and structure of the endocrine pancreas.