The Impact of Low-dose Gliclazide on the Incretin Effect and Indices of Beta-cell Function

AIMS/HYPOTHESIS: Studies in permanent neonatal diabetes suggest that sulphonylureas lower blood glucose without causing hypoglycemia, in part by augmenting the incretin effect. This mechanism has not previously been attributed to sulphonylureas in patients with type 2 diabetes (T2DM). We therefore aimed to evaluate the impact of low-dose gliclazide on beta-cell function and incretin action in patients with T2DM. METHODS: Paired oral glucose tolerance tests and isoglycemic infusions were performed to evaluate the difference in the classical incretin effect in the presence and absence of low-dose gliclazide in 16 subjects with T2DM (hemoglobin A1c < 64 mmol/mol, 8.0%) treated with diet or metformin monotherapy. Beta-cell function modeling was undertaken to describe the relationship between insulin secretion and glucose concentration. RESULTS: A single dose of 20 mg gliclazide reduced mean glucose during the oral glucose tolerance test from 12.01 ± 0.56 to 10.82 ± 0.5mmol/l [P = 0.0006; mean ± standard error of the mean (SEM)]. The classical incretin effect was augmented by 20 mg gliclazide, from 35.5% (lower quartile 27.3, upper quartile 61.2) to 54.99% (34.8, 72.8; P = 0.049). Gliclazide increased beta-cell glucose sensitivity by 46% [control 22.61 ± 3.94, gliclazide 33.11 ± 7.83 (P = 0.01)] as well as late-phase incretin potentiation [control 0.92 ± 0.05, gliclazide 1.285 ± 0.14 (P = 0.038)]. CONCLUSIONS/INTERPRETATION: Low-dose gliclazide reduces plasma glucose in response to oral glucose load, with concomitant augmentation of the classical incretin effect. Beta-cell modeling shows that low plasma concentrations of gliclazide potentiate late-phase insulin secretion and increase glucose sensitivity by 50%. Further studies are merited to explore whether low-dose gliclazide, by enhancing incretin action, could effectively lower blood glucose without risk of hypoglycemia

On the nature of the enigmatic object IRAS 19312+1950: A rare phase of massive star formation?

IRAS 19312+1950 is a peculiar object that has eluded firm characterization since its discovery, with combined maser properties similar to an evolved star and a young stellar object (YSO). To help determine its true nature, we obtained infrared spectra of IRAS 19312+1950 in the range 5-550 $\mu$m using the Herschel and Spitzer space observatories. The Herschel PACS maps exhibit a compact, slightly asymmetric continuum source at 170 $\mu$m, indicative of a large, dusty circumstellar envelope. The far-IR CO emission line spectrum reveals two gas temperature components: $\approx0.22M_{\odot}$ of material at $280\pm18$ K, and $\approx1.6M_{\odot}$ of material at $157\pm3$ K. The OI 63 $\mu$m line is detected on-source but no significant emission from atomic ions was found. The HIFI observations display shocked, high-velocity gas with outflow speeds up to 90 km s$^{-1}$ along the line of sight. From Spitzer spectroscopy, we identify ice absorption bands due to H$_2$O at 5.8 $\mu$m and CO$_2$ at 15 $\mu$m. The spectral energy distribution is consistent with a massive, luminous ($\sim2\times10^4L_{\odot}$) central source surrounded by a dense, warm circumstellar disk and envelope of total mass $\sim500$-$700M_{\odot}$, with large bipolar outflow cavities. The combination of distinctive far-IR spectral features suggest that IRAS 19312+1950 should be classified as an accreting high-mass YSO rather than an evolved star. In light of this reclassification, IRAS 19312+1950 becomes only the 5th high-mass protostar known to exhibit SiO maser activity, and demonstrates that 18 cm OH maser line ratios may not be reliable observational discriminators between evolved stars and YSOs.Comment: 16 pages. Accepted for publication in Ap

The EDIBLES Survey. VIII. Band profile alignment of diffuse interstellar bands

Context: There have been many attempts to identify families of diffuse interstellar bands (DIBs) with perfectly correlating band strengths. Although major efforts have been made to classify broadly based DIB families and important insights have been gained, no family has been identified with sufficient accuracy or statistical significance to prove that a series of selected DIBs originates from the same carrier. This can be attributed in part to the exclusive use of equivalent widths to establish DIB families. Aims: In a change of strategy, we search for DIBs that are highly correlated in both band strength and profile shape. This approach increases the chance of correlating DIBs being members of one family and originating from the same carrier molecule. We also search for correlations between DIB profile families and atomic interstellar lines, with the goal of further chemically constraining possible DIB carriers. Methods: We adapted the well-known method of time-series alignment to perform a spectral alignment; that is, DIB alignment. In a second step, we analysed the alignment results using a clustering analysis. This method required a statistically significant data set of DIB sight lines. The ESO Diffuse Interstellar Bands Large Exploration Survey (EDIBLES) data were perfectly suited for this application. Results: We report eight DIB families with correlating strengths and profiles, as well as four previously unreported DIBs in the visual range, found using DIB alignment. All profile family members show Pearson correlation coefficients in band strength higher than 0.9. In particular, we report the 6614 - 6521 AA DIB pair, in which both DIBs show the same triple-peak substructure and an unprecedented band strength Pearson correlation coefficient of 0.9935. The presented approach opens up new perspectives that can guide the laboratory search for DIB carriers.Comment: 53 pages, 53 figures, Accepted for publication in Astronomy & Astrophysic

The Gaia-ESO Survey : Extracting diffuse interstellar bands from cool star spectra: DIB-based interstellar medium line-of-sight structures at the kpc scale

Date of Acceptance: 05/10/2014Aims. We study how diffuse interstellar bands (DIBs) measured toward distance-distributed target stars can be used to locate dense interstellar (IS) clouds in the Galaxy and probe a line-of-sight (LOS) kinematical structure, a potentially useful tool when gaseous absorption lines are saturated or not available in the spectral range. Cool target stars are numerous enough for this purpose. Methods. We devised automated DIB-fitting methods appropriate for cool star spectra and multiple IS components. The data were fitted with a combination of a synthetic stellar spectrum, a synthetic telluric transmission, and empirical DIB profiles. The initial number of DIB components and their radial velocity were guided by HI 21 cm emission spectra, or, when available in the spectral range, IS neutral sodium absorption lines. For NaI, radial velocities of NaI lines and DIBs were maintained linked during a global simultaneous fit. In parallel, stellar distances and extinctions were estimated self-consistently by means of a 2D Bayesian method from spectroscopically-derived stellar parameters and photometric data. Results. We have analyzed Gaia-ESO Survey (GES) spectra of 225 stars that probe between ∼2 and 10 kpc long LOS in five different regions of the Milky Way. The targets are the two CoRoT fields, two open clusters (NGC 4815 and γ Vel), and the Galactic bulge. Two OGLE fields toward the bulge observed before the GES are also included (205 target stars). Depending on the observed spectral intervals, we extracted one or more of the following DIBs: λλ 6283.8, 6613.6, and 8620.4. For each field, we compared the DIB strengths with the Bayesian distances and extinctions, and the DIB Doppler velocities with the HI emission spectra. Conclusions. For all fields, the DIB strength and the target extinction are well correlated. For targets that are widely distributed in distance, marked steps in DIBs and extinction radial distance profiles match each other and broadly correspond to the expected locations of spiral arms. For all fields, the DIB velocity structure agrees with HI emission spectra, and all detected DIBs correspond to strong NaI lines. This illustrates how DIBs can be used to locate the Galactic interstellar gas and to study its kinematics at the kpc scale, as illustrated by Local and Perseus Arm DIBs that differ by ≳∼30 km s-1, in agreement with HI emission spectra. On the other hand, if most targets are located beyond the main absorber, DIBs can trace the differential reddening within the field.Peer reviewedFinal Accepted Versio

Charting Circumstellar Chemistry of Carbon-rich AGB Stars: I. ALMA 3 mm spectral surveys

AGB stars are major contributors to the chemical enrichment of the ISM through nucleosynthesis and extensive mass loss. Most of our current knowledge of AGB atmospheric and circumstellar chemistry, in particular in a C-rich environment, is based on observations of the carbon star IRC+10216. We aim to obtain a more generalised understanding of the chemistry in C-rich AGB CSEs by studying a sample of three carbon stars, IRAS15194-5115, IRAS15082-4808, and IRAS07454-7112, and test the archetypal status often attributed to IRC+10216. We performed spatially resolved, unbiased spectral surveys in ALMA Band 3. We identify a total of 132 rotational transitions from 49 molecular species. There are two main morphologies of the brightness distributions: centrally-peaked (e.g. HCN) and shell-like (e.g. C$_2$H). We estimated the sizes of the molecular emitting regions using azimuthally-averaged radial profiles of the line brightness distributions, and derived abundance estimates. Of the shell distributions, the cyanopolyynes peak at slightly smaller radii than the hydrocarbons, and CN and HNC show the most extended emission. The emitting regions for each species are the smallest for IRAS07454-7112. We find that, within the uncertainties of the analysis, the three stars present similar abundances for most species, also compared to IRC+10216. We find that SiO is more abundant in our three stars compared to IRC+10216. Our estimated isotopic ratios match well the literature values for the sources. The observed circumstellar chemistry appears very similar across our sample and compared to that of IRC+10216, both in terms of the relative location of the emitting regions and molecular abundances. This implies that, to a first approximation, the chemical models tailored to IRC+10216 are able to reproduce the observed chemistry in C-rich envelopes across roughly an order of magnitude in wind density.Comment: 21 pages. 13 figures and 8 tables in the main text. 5 appendices contain additional figures and tables. Appendix tables are available in electronic form at the CDS, along with the reprocessed ALMA cubes and spectra, at http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/ or via anonymous ftp to cdsarc.u-strasbg.fr(130.79.128.5). Accepted for publication in Astronomy & Astrophysic

The EDIBLES Survey. VII. A survey of C2 and C3 in interstellar clouds

We carried out a sensitive survey of C$_2$ and C$_3$ using the EDIBLES data set. We also expanded our searches to C$_4$, C$_5$, and $^{13}$C$^{12}$C isotopologue in the most molecule-rich sightlines. We fit synthetic spectra generated following a physical excitation model to the C$_2$ (2-0) Phillips band to obtain the C$_2$ column density ($N$) as well as the kinetic temperature ($T_\textrm{kin}$) and number density ($n$) of the host cloud. The C$_3$ molecule was measured through its $\tilde{A} - \tilde{X}$ (000-000) electronic origin band system. We simulated the excitation of this band with a double-temperature Boltzmann distribution. We present the largest combined survey of C$_2$ and C$_3$ to date in which the individual transitions can be resolved. In total we detected C$_2$ in 51 velocity components along 40 sightlines, and C$_3$ in 31 velocity components along 27 sightlines. The two molecules are detected in the same velocity components. We find a very good correlation between $N$(C$_2$) and $N$(C$_3$) with Pearson $r = 0.93$ and an average $N$(C$_2$)/$N$(C$_3$) ratio of 15.5$\pm$1.4. A comparison with the behaviour of the C$_2$ DIBs shows that there are no clear differences among sightlines with and without detection of C$_2$ and C$_3$. This is in direct contrast to the better-studied non-C$_2$ DIBs who have reduced strengths in molecule-rich environments. We also identify for the first time the $Q$(2), $Q$(3), and $Q$(4) transitions of the $^{13}$C$^{12}$C (2-0) Phillips band in a stacked average spectrum, and estimate the isotopic ratio of carbon $^{12}$C/$^{13}$C as 79$\pm$8. Our search for the C$_4$ and C$_5$ optical bands was unsuccessful.Comment: 31 pages, 23 figures. To appear in A&

The EDIBLES survey III. C2-DIBs and their profiles

Context. An unambiguous identification of the carriers of the diffuse interstellar bands (DIBs) would provide important clues to the life cycle of interstellar matter. The so-called C2-DIBs are a class of very weak bands that fall in the blue part of the optical spectrum and are associated with high column densities of the C2 molecule. DIB profile structures constrain potential molecular carriers, but their measurement requires high signal-to-noise, high-resolution spectra and the use of sightlines without Doppler splitting, as typical for a single-cloud situation. Aims. Spectra from the ESO Diffuse Interstellar Bands Large Exploration Survey (EDIBLES) conducted at the Very Large Telescope (ESO/Paranal) were explored to identify single-cloud and high C2 column sightlines, extract the corresponding C2-DIBs and study their strengths and profiles, and to investigate in detail any sub-structures. Methods. The target selection was made based on profile-fitting of the 3303 and 5895 Å Nai doublets and the detection of C2 lines. The C2 (2-0) (8750–8849 Å) Phillips system was fitted using a physical model of the host cloud. C2 column densities, temperatures as well as gas densities were derived for each sightline. Results. Eighteen known C2-DIBs and eight strong non-C2 DIBs were extracted towards eight targets, comprising seven single-cloud and one multi-cloud line-of-sights. Correlational studies revealed a tight association of the former group with the C2 columns, whereas the non-C2 DIBs are primarily correlated with reddening. We report three new weak diffuse band candidates at 4737.5, 5547.4 and 5769.8 Å. We show for the first time that at least 14 C2-DIBs exhibit spectral sub-structures which are consistent with unresolved rotational branches of molecular carriers. The variability of their peak separations among the bands for a given sightline implies that their carriers are different molecules with quite different sizes. We also illustrate how profiles of the same DIB vary among targets and as a function of physical parameters, and provide tables defining the sub-structures to be compared with future models and experimental results

No phosphine in the atmosphere of Venus

The detection of phosphine (PH₃) has been recently reported in the atmosphere of Venus employing mm-wave radio observations (Greaves et at. 2020). We here demonstrate that the observed PH₃ feature with JCMT can be fully explained employing plausible mesospheric SO₂ abundances (~100 ppbv as per the SO₂ profile given in their figure 9), while the identification of PH₃ in the ALMA data should be considered invalid due to severe baseline calibration issues. We demonstrate this by independently calibrating and analyzing the ALMA data using different interferometric analysis tools, in which we observe no PH₃ in all cases. Furthermore, for any PH₃ signature to be produced in either ALMA or JCMT spectra, PH₃ needs to present at altitudes above 70 km, in stark disagreement with their photochemical network. We ultimately conclude that this detection of PH₃ in the atmosphere of Venus is not supported by our analysis of the data

Multi-epoch high-resolution spectroscopy of SN2011fe - Linking the progenitor to its environment

This study attempts to establish a link between the reasonably well known nature of the progenitor of SN2011fe and its surrounding environment. This is done with the aim of enabling the identification of similar systems in the vast majority of the cases, when distance and epoch of discovery do not allow a direct approach. To study the circumstellar environment of SN2011fe we have obtained high-resolution spectroscopy of SN2011fe on 12 epochs, from 8 to 86 days after the estimated date of explosion, targeting in particular at the time evolution of CaII and NaI. Three main absorption systems are identified from CaII and NaI, one associated to the Milky Way, one probably arising within a high-velocity cloud, and one most likely associated to the halo of M101. The Galactic and host galaxy reddening, deduced from the integrated equivalent widths (EW) of the NaI lines are E(B-V)=0.011+/-0.002 and E(B-V)=0.014+/-0.002 mag, respectively. The host galaxy absorption is dominated by a component detected at the same velocity measured from the 21-cm HI line at the projected SN position (~180 km/s). During the ~3 months covered by our observations, its EW changed by 15.6+/-6.5 mA. This small variation is shown to be compatible with the geometric effects produced by therapid SN photosphere expansion coupled to the patchy fractal structure of the ISM. The observed behavior is fully consistent with ISM properties similar to those derived for our own Galaxy, with evidences for structures on scales <100 AU. SN2011fe appears to be surrounded by a "clean" environment. The lack of blue-shifted, time-variant absorption features is fully consistent with the progenitor being a binary system with a main-sequence, or even another degenerate star.Comment: 12 pages, 6 figures, submitted to Astronomy and Astrophysic