6,807 research outputs found
Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues
Chronic intermittent hypoxia (CIH) inhibits plasma lipoprotein clearance and adipose lipoprotein lipase (LPL) activity in association with upregulation of an LPL inhibitor angiopoietin-like protein 4 (Angptl4). We hypothesize that CIH inhibits triglyceride (TG) uptake via Angptl4 and that an anti-Angptl4-neutralizing antibody would abolish the effects of CIH. Male C57BL/6J mice were exposed to four weeks of CIH or intermittent air (IA) while treated with Ab (30 mg/kg ip once a week). TG clearance was assessed by [H 3 ]triolein administration retroorbitally. CIH delayed TG clearance and suppressed TG uptake and LPL activity in all white adipose tissue depots, brown adipose tissue, and lungs, whereas heart, liver, and spleen were not affected. CD146+ CD11b α pulmonary microvascular endothelial cells were responsible for TG uptake in the lungs and its inhibition by CIH. Antibody to Angptl4 decreased plasma TG levels and increased TG clearance and uptake into adipose tissue and lungs in both control and CIH mice to a similar extent, but did not reverse the effects of CIH. The antibody reversed the effects of CIH on LPL in adipose tissue and lungs. In conclusion, CIH inactivates LPL by upregulating Angptl4, but inhibition of TG uptake occurs predominantly via an Angptl4/LPL-independent mechanism
β-Cell Hyperplasia Induced by Hepatic Insulin Resistance: Role of a Liver-Pancreas Endocrine Axis Through Insulin Receptor A Isoform
Objective: Type 2 diabetes results from a combination of insulin resistance and impaired insulin secretion. To directly address the effects of hepatic insulin resistance in adult animals, we developed an inducible liver-specific insulin receptor knockout mouse (iLIRKO). Research Design and Methods: Using this approach, we were able to induce variable insulin receptor (IR) deficiency in a tissue-specific manner (liver mosaicism). Results: iLIRKO mice presented progressive hepatic and extrahepatic insulin resistance without liver dysfunction. Initially, iLIRKO mice displayed hyperinsulinemia and increased -cell mass, the extent of which was proportional to the deletion of hepatic IR. Our studies of iLIRKO suggest a cause-and-effect relationship between progressive insulin resistance and the fold increase of plasma insulin levels and -cell mass. Ultimately, the -cells failed to secrete sufficient insulin, leading to uncontrolled diabetes. We observed that hepatic IGF-1 expression was enhanced in iLIRKO mice, resulting in an increase of circulating IGF-1. Concurrently, the IR-A isoform was upregulated in hyperplastic -cells of iLIRKO mice and IGF-1–induced proliferation was higher than in the controls. In mouse -cell lines, IR-A, but not IR-B, conferred a proliferative capacity in response to insulin or IGF-1, providing a potential explanation for the -cell hyperplasia induced by liver insulin resistance in iLIRKO mice. Conclusions: Our studies of iLIRKO mice suggest a liver-pancreas endocrine axis in which IGF-1 functions as a liver-derived growth factor to promote compensatory pancreatic islet hyperplasia through IR-A
Search for muon-neutrino emission from GeV and TeV gamma-ray flaring blazars using five years of data of the ANTARES telescope
The ANTARES telescope is well-suited for detecting astrophysical transient
neutrino sources as it can observe a full hemisphere of the sky at all times
with a high duty cycle. The background due to atmospheric particles can be
drastically reduced, and the point-source sensitivity improved, by selecting a
narrow time window around possible neutrino production periods. Blazars, being
radio-loud active galactic nuclei with their jets pointing almost directly
towards the observer, are particularly attractive potential neutrino point
sources, since they are among the most likely sources of the very high-energy
cosmic rays. Neutrinos and gamma rays may be produced in hadronic interactions
with the surrounding medium. Moreover, blazars generally show high time
variability in their light curves at different wavelengths and on various time
scales. This paper presents a time-dependent analysis applied to a selection of
flaring gamma-ray blazars observed by the FERMI/LAT experiment and by TeV
Cherenkov telescopes using five years of ANTARES data taken from 2008 to 2012.
The results are compatible with fluctuations of the background. Upper limits on
the neutrino fluence have been produced and compared to the measured gamma-ray
spectral energy distribution.Comment: 27 pages, 16 figure
Urticarial vasculitis in northern Spain: clinical study of 21 cases
Urticarial vasculitis (UV) is a subset of cutaneous vasculitis (CV), characterized clinically by urticarial skin lesions of more than 24 hours' duration and histologically by leukocytoclastic vasculitis. We assessed the frequency, clinical features, treatment, and outcome of a series of patients with UV. We conducted a retrospective study of patients with UV included in a large series of unselected patients with CV from a university hospital. Of 766 patients with CV, UV was diagnosed in 21 (2.7%; 9 male and 12 female patients; median age, 35 yr; range, 1-78 yr; interquartile range, 5-54 yr). Eight of the 21 cases were aged younger than 20 years old. Potential precipitating factors were upper respiratory tract infections and drugs (penicillin) (n = 4; in all cases in patients aged <20 yr), human immunodeficiency virus (HIV) infection (n = 1), and malignancy (n = 1). Besides urticarial lesions, other features such as palpable purpura (n = 7), arthralgia and/or arthritis (n = 13), abdominal pain (n = 2), nephropathy (n = 2), and peripheral neuropathy (n = 1) were observed. Hypocomplementemia (low C4) with low C1q was disclosed in 2 patients. Other abnormal laboratory findings were leukocytosis (n = 7), increased erythrocyte sedimentation rate (n = 6), anemia (n = 4), and antinuclear antibody positivity (n = 2). Treatment included corticosteroids (n = 12), antihistaminic drugs (n = 6), chloroquine (n = 4), nonsteroidal antiinflammatory drugs (n = 3), colchicine (n = 2), and azathioprine (n = 1). After a median follow-up of 10 months (interquartile range, 2-38 mo) recurrences were observed in 4 patients. Apart from 1 patient who died because of an underlying malignancy, the outcome was good with full recovery in the remaining patients. In conclusion, our results indicate that UV is rare but not exceptional. In children UV is often preceded by an upper respiratory tract infection. Urticarial lesions and joint manifestations are the most frequent clinical manifestation. Low complement serum levels are observed in a minority of cases. The prognosis is generally good, but depends on the underlying disease
Incretins in patients with rheumatoid arthritis
Background: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. Methods: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects. Results: Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (? coefficient 46, 95% CI 6?87, p = 0.026) and Clinical Disease Activity Index (? coefficient 7.74, 95% CI 1.29?14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with ?-cell function (HOMA2 of ?-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response. Conclusions: The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA.This work was supported by grants from the Spanish Ministry of Health,
Subdirección General de Evaluación y Fomento de la Investigación, Plan
Estatal de Investigación Científica y Técnica y de Innovación 2013–2016
Instituto de Salud Carlos III [ISCIII] PI14/00394) and by the Fondo Europeo de
Desarrollo Regional (FEDER) (to IFA). The research of MAGG was supported
by European Union FEDER funds and by the “Fondo de Investigación
Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060, and PI15/00525) of the
Instituto de Salud Carlos III (ISCIII; Spanish Health Ministry). The research of
MAGG was also partially supported by RETICS Programs RD12/0009 (RIER)
and RD12/0009/0013 from the ISCIII (Spanish Health Ministry)
A search for charged massive long-lived particles
We report on a search for charged massive long-lived particles (CMLLPs),
based on 5.2 fb of integrated luminosity collected with the D0 detector
at the Fermilab Tevatron collider. We search for events in which one
or more particles are reconstructed as muons but have speed and ionization
energy loss inconsistent with muons produced in beam collisions.
CMLLPs are predicted in several theories of physics beyond the standard model.
We exclude pair-produced long-lived gaugino-like charginos below 267 GeV and
higgsino-like charginos below 217 GeV at 95% C.L., as well as long-lived scalar
top quarks with mass below 285 GeV.Comment: submitted to Phys. Rev. Letter
Search for single vector-like quarks in ppbar collisions at sqrt(s) = 1.96 TeV
We present a search for hypothetical vector-like quarks in ppbar collisions
at sqrt(s) = 1.96 TeV. The data were collected by the D0 detector at the
Fermilab Tevatron Collider and correspond to an integrated luminosity of 5.4
fb^(-1). We select events with a final state composed of a W or Z boson and a
jet consistent with a heavy object decay. We observe no significant excess in
comparison to the background prediction and set limits on production cross
sections for vector-like quarks decaying to W+jet and Z+jet. These are the most
stringent mass limits for electroweak single vector-like quark production at
hadron colliders.Comment: submitted to Phys. Rev. Let
Search for W' bosons decaying to an electron and a neutrino with the D0 detector
This Letter describes the search for a new heavy charged gauge boson W'
decaying into an electron and a neutrino. The data were collected with the D0
detector at the Fermilab Tevatron proton-antiproton Collider at a
center-of-mass energy of 1.96 TeV, and correspond to an integrated luminosity
of about 1 inverse femtobarn. Lacking any significant excess in the data in
comparison with known processes, an upper limit is set on the production cross
section times branching fraction, and a W' boson with mass below 1.00 TeV can
be excluded at the 95% C.L., assuming standard-model-like couplings to
fermions. This result significantly improves upon previous limits, and is the
most stringent to date.Comment: submitted to Phys. Rev. Let
Measurement of spin correlation in ttbar production using a matrix element approach
correlation, assuming that the spin of the top quark is either correlated
with the spin of the anti-top quark as predicted by the standard model or is
uncorrelated. For the first time we use a matrix-element-based approach to
study ttbar spin correlation. We use {ttbar -> W+bW-bbar ->l+nubl-nub} final
states produced in ppbar collisions at a center of mass energy sqrt(s)=1.96
TeV, where l denotes an electron or a muon. The data correspond to an
integrated luminosity of 5.4 fb-1 and were collected with the dzero detector at
the Fermilab Tevatron collider. The result agrees with the standard model
prediction. We exclude the hypothesis that the spins of the ttbar are
uncorrelated at the 97.7% C.L.Comment: 7 pages, 3 figures, submitted to Phys. Rev. Let
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