Evidence against a role for insulin-signaling proteins PI 3-kinase and Akt in insulin resistance in human skeletal muscle induced by short-term GH infusion

Prolonged growth hormone (GH) excess is known to be associated with insulin resistance, but the underlying mechanisms remain unknown. The aim of this study was to assess the impact of GH on insulin-stimulated glucose metabolism and insulin signaling in human skeletal muscle. In a cross-over design, eight healthy male subjects (age 26.0 +/- 0.8 yr and body mass index 24.1 +/- 0.5 kg/m2) were infused for 360 min with either GH (Norditropin, 45 ng.kg(-1).min(-1)) or saline. During the final 180 min of the infusion, a hyperinsulinemic euglycemic clamp was performed (insulin infusion rate: 1.2 mU.kg(-1).min(-1)). Muscle biopsies from vastus lateralis were taken before GH/saline administration and after 60 min of hyperinsulinemia. GLUT4 content and insulin signaling, as assessed by insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase and Akt activity were determined. GH levels increased to a mean (+/-SE) level of 20.0 +/- 2.3 vs. 0.5 +/- 0.2 microg/l after saline infusion (P < 0.01). During GH infusion, the glucose infusion rate during hyperinsulinemia was reduced by 38% (P < 0.01). In both conditions, free fatty acids were markedly suppressed during hyperinsulinemia. Despite skeletal muscle insulin resistance, insulin still induced a similar approximately 3-fold rise in IRS-1-associated PI 3-kinase activity (269 +/- 105 and 311 +/- 71% compared with baseline, GH vs. saline). GH infusion did not change Akt protein expression, and insulin caused an approximately 13-fold increase in Akt activity (1,309 +/- 327 and 1,287 +/- 173%) after both GH and saline infusion. No difference in total GLUT4 content was noted (114.7 +/- 7.4 and 107.6 +/- 16.7 arbitrary units, GH vs. saline, compared with baseline). In conclusion, insulin resistance in skeletal muscle induced by short-term GH administration is not associated with detectable changes in the upstream insulin-signaling cascade or reduction in total GLUT4. Yet unknown mechanisms in insulin signaling downstream of Akt may be responsible.     

RBT--a tool for building refined Buneman trees

SUMMARY: We have developed a tool implementing an efficient algorithm for refined Buneman tree reconstruction. The algorithm--which has the same complexity as the neighbour-joining method and the (plain) Buneman tree construction--enables refined Buneman tree reconstruction on large taxa sets. AVAILABILITY: The source code for RBT, written in Java, is available under the GNU Public License (GPL) at http://www.birc.dk/Software/RBT CONTACT: besen@daimi.au.dk.     

The Role of Convictions and Trust for Public Protest Potential in the Case of Carbon Dioxide Capture and Storage (CCS)

For the public to accept new technologies, trust and convictions play an important role. In the present research, we used structural equation modeling to examine an extensive causal model of the role of convictions and trust for the public's protest potential against carbon dioxide capture and storage (CCS) among a large sample of the general population (N = 769). Trust, convictions, perceived benefits, and risks were included in the model. Our model fitted the data well. Convictions regarding emission reduction, decentralization of energy production, and tampering with natural structures in the deep subsurface influenced the perception of benefits and risks. Trust, in contrast, was barely influential. Perceived benefits were more prominent for public protest potential than perceived risks. However, perceived benefits did not dominate perceived risks as much as earlier studies found for acceptance. We argue that trust can become fully effective as a determinant of perceived risks and benefits only when the public perceives the distinct positioning of the stakeholders involved. Until then, laypeople are likely to draw on their own convictions and intuitive mental concepts for making decisions about accepting a new technology or protesting it.     

Automated lab-scale production of PVA/PEG-enzyme immobilisates

Entrapment of biocatalysts by cryogelation is a gentle method to extend the scope of biocatalysis. To foster the use of this versatile method we devised an automated injector for the production of PVA/PEG beads. The device consists of a thermostated reservoir connected to a programmable injector nozzle and an agitated receiving bath for the droplets. This lab-scale production unit yields up to 1500 beads with immobilized enzyme per minute with a narrow size distribution and good roundness.     

Adolescents with Type 1 Diabetes – The Impact of Gender,Age, and Health-Related Functioning on Eating Disorder Psychopathology

Objective

To investigate correlates of eating disorder psychopathology in adolescent males and females with type 1 diabetes.

Method

A total of 105 adolescents with type 1 diabetes (42% males), aged 12–20 years, were recruited from the Norwegian Childhood Diabetes Registry in this population-based study. All participants were interviewed with the Child Eating Disorder Examination. Additionally, the Brief Illness Perception Questionnaire, the Adolescent Coping Orientation for Problem Experiences and the Beliefs about Medicines Questionnaire were administered to assess health-related functioning. Clinical data were obtained from the Norwegian Childhood Diabetes Registry.

Results

Significant gender differences were demonstrated in the pattern of correlates of eating disorder pathology. Among females, eating disorder psychopathology was significantly associated with body mass index adjusted for age and gender, age, insulin restriction, coping, illness perceptions, and perceptions of insulin concern. In a regression model, age, illness perceptions, and insulin restriction remained significantly associated with eating disorder psychopathology, explaining 48% of the variance. None of the variables were associated with eating disorder psychopathology among males.

Discussion

Greater clinical awareness of illness perceptions, attitudes toward insulin, and insulin restriction may potentially decrease the risk of developing eating disorders among female adolescents with type 1 diabetes, and the subsequent increased morbidity and mortality associated with comorbid type 1 diabetes and eating disorders.     

Coping with fast climate change in northern ecosystems: mechanisms underlying the population‐level response of a specialist avian predator

Northern ecosystems are facing unprecedented climate modifications, which pose a major threat for arctic species, especially the specialist predator guild. However, the mechanisms underlying responses of predators to climate change remain poorly understood. Climate can influence fitness parameters of predators either through reduced reproduction or survival following adverse weather conditions, or via changes in the population dynamics of their main prey. Here, we combined three overlapping long‐term datasets on the breeding density and parameters of a rodent‐specialist predator, the rough‐legged buzzard Buteo lagopus, its main prey population dynamics and climate variables, collected in subarctic areas of Finland and Norway, to assess the impact of changing climate on the predator reproductive response. Rough‐legged buzzards responded to ongoing climate change by advancing their laying date (0.1 d yr^?1 over the 21 yr of the study period), as a consequence of earlier snowmelt. However, we documented for the same period a decrease in breeding success, which principally resulted from an indirect effect of changes in the dynamics of their main prey, i.e. grey‐sided voles Microtus oeconomus, and not from the expected negative effect of unfavorable weather conditions during the brood‐rearing period on nestling survival. Additionally, we showed the striking impact of autumn and winter weather conditions on vole population growth rates in subarctic ecosystems, with a strong positive correlation between mean snow depth in autumn and winter and both winter and summer population growth rates. Our results highlighted that, in northern ecosystems, ongoing climate change has the potential to impact specialist predator species through two mechanistic linkages, which may in the long‐run, threaten the viability of their populations, and lead to potential severe cascading trophic effects at the ecosystem level.     

Burden of Hospital Admission and Repeat Angiography in Angina Pectoris Patients with and without Coronary Artery Disease: A Registry-Based Cohort Study

Aims

To evaluate risk of hospitalization due to cardiovascular disease (CVD) and repeat coronary angiography (CAG) in stable angina pectoris (SAP) with no obstructive coronary artery disease (CAD) versus obstructive CAD, and asymptomatic reference individuals.

Methods and Results

We followed 11,223 patients with no prior CVD having a first-time CAG in 1998–2009 due to SAP symptoms and 5,695 asymptomatic reference individuals from the Copenhagen City Heart Study through registry linkage for 7.8 years (median). In recurrent event survival analysis, patients with SAP had 3–4-fold higher risk of hospitalization for CVD irrespective of CAG findings and cardiovascular comorbidity. Multivariable adjusted hazard ratios(95%CI) for patients with angiographically normal coronary arteries was 3.0(2.5–3.5), for angiographically diffuse non-obstructive CAD 3.9(3.3–4.6) and for 1–3-vessel disease 3.6–4.1(range)(all P<0.001). Mean accumulated hospitalization time was 3.5(3.0–4.0)(days/10 years follow-up) in reference individuals and 4.5(3.8–5.2)/7.0(5.4–8.6)/6.7(5.2–8.1)/6.1(5.2–7.4)/8.6(6.6–10.7) in patients with angiographically normal coronary arteries/angiographically diffuse non-obstructive CAD/1-, 2-, and 3-vessel disease, respectively (all P<0.05, age-adjusted). SAP symptoms predicted repeat CAG with multivariable adjusted hazard ratios for patients with angiographically normal coronary arteries being 2.3(1.9–2.9), for angiographically diffuse non-obstructive CAD 5.5(4.4–6.8) and for obstructive CAD 6.6–9.4(range)(all P<0.001).

Conclusions

Patients with SAP symptoms and angiographically normal coronary arteries or angiographically diffuse non-obstructive CAD suffer from considerably greater CVD burdens in terms of hospitalization for CVD and repeat CAG compared with asymptomatic reference individuals even after adjustment for cardiac risk factors and exclusion of cardiovascular comorbidity as cause. Contrary to common perception, excluding obstructive CAD by CAG in such patients does not ensure a benign cardiovascular prognosis.