Glucagon and glucagon-like peptide-1 (GLP-1) are evolutionarily related anorectic hormones. Glucagon also increases energy expenditure. The combination of glucagon and GLP-1 could cause weight loss ...through a simultaneous reduction in food intake and increased energy expenditure. However, the effect of combined administration of glucagon and GLP-1 on food intake and neuronal activation has not previously been studied. Furthermore, the effect of glucagon on neuronal activation in appetite regulating centres has not been assessed. Characterisation of the effects of glucagon when administered singly and in combination with GLP-1 on neuronal activation will be important for determining the mechanism of action of related potential antiobesity therapies.
To investigate the effects of peripherally administered GLP-1 and glucagon on food intake, neuronal activation and blood glucose in mice when administered individually and in combination.
Food intake, blood glucose and c-fos expression in the hypothalamus, amygdala and brainstem were measured in response to GLP-1 and glucagon, alone and in combination.
Peripherally administered GLP-1 and glucagon decreased food intake and increased c-fos expression in the brainstem and amygdala. Doses of GLP-1 and glucagon that individually did not significantly affect feeding, in combination were anorectic and stimulated neuronal activation in the area postrema (AP) and central nucleus of the amygdala. Combined administration of GLP-1 and glucagon prevented the acute hyperglycemic effect of glucagon alone.
Anorectic doses of glucagon and GLP-1 induced similar patterns of c-fos expression. Combined administration of low dose GLP-1 and glucagon inhibited food intake and induced c-fos expression in the AP and amygdala. The combination of both hormones may offer the opportunity to utilise the beneficial effects of reduced food intake and increased energy expenditure, and may therefore be a potential treatment for obesity.
ABSTRACT We present late time multi-wavelength observations of Swift J1644+57, suggested to be a relativistic tidal disruption flare (TDF). Our observations extend to >4 years from discovery and show ...that 1.4 years after outburst the relativistic jet switched off on a timescale less than tens of days, corresponding to a power-law decay faster than t−70. Beyond this point weak X-rays continue to be detected at an approximately constant luminosity of LX ∼ 5 × 1042 erg s−1 and are marginally inconsistent with a continuing decay of t−5/3, similar to that seen prior to the switch-off. Host photometry enables us to infer a black hole mass of MBH = 3 × 106 M , consistent with the late time X-ray luminosity arising from sub-Eddington accretion onto the black hole in the form of either an unusually optically faint active galactic nucleus or a slowly varying phase of the transient. Optical/IR observations show a clear bump in the light curve at timescales of 30-50 days, with a peak magnitude (corrected for host galaxy extinction) of MR ∼ −22 to −23. The luminosity of the bump is significantly higher than seen in other, non-relativistic TDFs and does not match any re-brightening seen at X-ray or radio wavelengths. Its luminosity, light curve shape, and spectrum are broadly similar to those seen in superluminous supervnovae, although subject to large uncertainties in the correction of the significant host extinction. We discuss these observations in the context of both TDF and massive star origins for Swift J1644+5734 and other candidate relativistic tidal flares.
The first gamma-ray burst (GRB) confirmed to be bright enough to be seen with the naked eye, GRB 080319B at redshift z = 0.937, allowed for exquisite follow-up observations across the electromagnetic ...spectrum. We present our detailed optical and infrared (IR) observations of the afterglow, consisting of over 5000 images starting 51 s after the GRB trigger, in concert with our own analysis of the Swift UVOT, Burst Alert Telescope (BAT), and XRT data. The event is extreme not only in observed properties but also intrinsically: it was the most luminous event ever recorded at optical and IR wavelengths and had an exceedingly high isotropic-equivalent energy release in gamma -rays. At early times, the afterglow evolution is broadly consistent with being reverse-shock dominated, but then is subsumed by a forward shock at around 1000 s. The overall spectral energy distribution, spanning from ultraviolet through near-IR wavelengths, shows no evidence for a significant amount of dust extinction in the host frame. The afterglow evolution, however, is highly chromatic: starting at about 1000 s the index shifts blueward before shifting back to the red at late times. In our deepest late-time observations, we find tentative evidence for an optical jet break and a luminous supernova. Finally, we examine the detectability of such events with current and future facilities and find that such an event could be detected in gamma rays by BAT out to z = 10.7 (8 sigma ), while the nominal EXIST sensitivity would allow detection to z 32. At the K band, this source would have been easily detected with meter-class telescopes to z 17.
The rapid succession of discoveries of short-duration hard-spectrum gamma-ray bursts (GRBs) has led to unprecedented insights into the energetics of the explosion and nature of the progenitors. Yet ...short of the detection of a smoking gun, such as a burst of coincident gravitational radiation or a Li-Paczynski minisupernova, it is unlikely that a definitive claim can be made for the progenitors. As was the case with long-duration soft-spectrum GRBs, however, the expectation is that a systematic study of the hosts and locations of short GRBs could begin to yield fundamental clues as to their nature. We present an aggregate study of the host galaxies of short-duration hard-spectrum GRBs. In particular, we present the Gemini-North and Keck discovery spectra of the galaxies that hosted three short GRBs and a moderate-resolution (R - 6000) spectrum of a fourth host. We find that these short-hard GRBs originate in a variety of low-redshift (z < 1) environments that differ substantially from those of long-soft GRBs, both on individual galaxy scales and on galaxy-cluster scales. Specifically, three of the bursts are found to be associated with old and massive galaxies with no current (<0.1 M sub( )yr super(-1)) or recent star formation. Two of these galaxies are located within a cluster environment. These observations support an origin from the merger of compact stellar remnants, such as double neutron stars or a neutron star-black hole binary. The fourth event, in contrast, occurred within a dwarf galaxy with a star formation rate exceeding 0.3 M sub( )yr super(-1). Therefore, it appears that like supernovae of Type la, the progenitors of short-hard bursts are created in all galaxy types, suggesting a corresponding class with a wide distribution of delay times between formation and explosion.
We present extensive early photometric (ultraviolet through near-infrared) and spectroscopic (optical and near-infrared) data on supernova (SN) 2008D as well as X-ray data analysis on the associated ...Swift X-ray transient (XRT) 080109. Our data span a time range of 5 hr before the detection of the X-ray transient to 150 days after its detection, and a detailed analysis allowed us to derive constraints on the nature of the SN and its progenitor; throughout we draw comparisons with results presented in the literature and find several key aspects that differ. We show that the X-ray spectrum of XRT 080109 can be fit equally well by an absorbed power law or a superposition of about equal parts of both power law and blackbody. Our data first established that SN 2008D is a spectroscopically normal SN Ib (i.e., showing conspicuous He lines) and showed that SN 2008D had a relatively long rise time of 18 days and a modest optical peak luminosity. The early-time light curves of the SN are dominated by a cooling stellar envelope (for Delta *Dt0.1-4 days, most pronounced in the blue bands) followed by 56Ni decay. We construct a reliable measurement of the bolometric output for this stripped-envelope SN, and, combined with estimates of E K and M ej from the literature, estimate the stellar radius R of its probable Wolf-Rayet progenitor. According to the model of Waxman et al. and Chevalier & Fransson, we derive R W07 = 1.2 +/- 0.7R and R CF08 = 12 +/- 7 R, respectively; the latter being more in line with typical WN stars. Spectra obtained at three and four months after maximum light show double-peaked oxygen lines that we associate with departures from spherical symmetry, as has been suggested for the inner ejecta of a number of SN Ib cores.
We present early optical photometry and spectroscopy of the afterglow and host galaxy of the bright short-duration gamma-ray burst GRB 130603B discovered by the Swift satellite. We find that while ...the host is a relatively luminous (L approximately 0.8 L* sub(B)), star-forming (SFR = 1.84 M sub(middot in circle) yr super(-1)) galaxy with almost solar metallicity, the spectrum of the afterglow exhibits weak Ca II absorption features but negligible emission features. The explosion site therefore lacks evidence of recent star formation, consistent with the relatively long delay time distribution expected in a compact binary merger scenario. The star formation rate (SFR; both in an absolute sense and normalized to the luminosity) and metallicity of the host are both consistent with the known sample of short-duration GRB hosts and with recent results which suggest GRB 130603B emission to be the product of the decay of radioactive species produced during the merging process of a neutron-star-neutron-star binary ("kilonova").
We present a sample of 77 optical afterglows (OAs) of Swift detected gamma-ray bursts (GRBs) for which spectroscopic follow-up observations have been secured. Our first objective is to measure the ...redshifts of the bursts. For the majority (90%) of the afterglows, the redshifts have been determined from the spectra. We provide line lists and equivalent widths (EWs) for all detected lines redward of Ly Delta *a covered by the spectra. In addition to the GRB absorption systems, these lists include line strengths for a total of 33 intervening absorption systems. We discuss to what extent the current sample of Swift bursts with OA spectroscopy is a biased subsample of all Swift detected GRBs. For that purpose we define an X-ray-selected statistical sample of Swift bursts with optimal conditions for ground-based follow-up from the period 2005 March to 2008 September; 146 bursts fulfill our sample criteria. We derive the redshift distribution for the statistical (X-ray selected) sample and conclude that less than 18% of Swift bursts can be at z > 7. We compare the high-energy properties (e.g., Delta *g-ray (15-350 keV) fluence and duration, X-ray flux, and excess absorption) for three subsamples of bursts in the statistical sample: (1) bursts with redshifts measured from OA spectroscopy; (2) bursts with detected optical and/or near-IR afterglow, but no afterglow-based redshift; and (3) bursts with no detection of the OA. The bursts in group (1) have slightly higher Delta *g-ray fluences and higher X-ray fluxes and significantly less excess X-ray absorption than bursts in the other two groups. In addition, the fractions of dark bursts, defined as bursts with an optical to X-ray slope Delta *bOX < 0.5, is 14% in group (1), 38% in group (2), and >39% in group (3). For the full sample, the dark burst fraction is constrained to be in the range 25%-42%. From this we conclude that the sample of GRBs with OA spectroscopy is not representative for all Swift bursts, most likely due to a bias against the most dusty sight lines. This should be taken into account when determining, e.g., the redshift or metallicity distribution of GRBs and when using GRBs as a probe of star formation. Finally, we characterize GRB absorption systems as a class and compare them to QSO absorption systems, in particular the damped Ly Delta *a absorbers (DLAs). On average GRB absorbers are characterized by significantly stronger EWs for H I as well as for both low and high ionization metal lines than what is seen in intervening QSO absorbers. However, the distribution of line strengths is very broad and several GRB absorbers have lines with EWs well within the range spanned by QSO-DLAs. Based on the 33 z > 2 bursts in the sample, we place a 95% confidence upper limit of 7.5% on the mean escape fraction of ionizing photons from star-forming galaxies.
The responses of the gut hormone peptide YY (PYY) to food were investigated in 20 normal-weight and 20 obese humans in response to six test meals of varying calorie content. Human volunteers had a ...graded rise in plasma PYY (R2 = 0.96; P < 0.001) during increasing calorific meals, but the obese subjects had a lower endogenous PYY response at each meal size (P < 0.05 at all levels). The ratio of plasma PYY1–36 to PYY3–36 was similar in normal-weight and obese subjects. The effect on food intake and satiety of graded doses of exogenous PYY3–36 was also evaluated in 12 human volunteers. Stepwise increasing doses of exogenous PYY3–36 in humans caused a graded reduction in food intake (R2 = 0.38; P < 0.001). In high-fat-fed (HF) mice that became obese and low-fat-fed mice that remained normal weight, we measured plasma PYY, tissue PYY, and PYY mRNA levels and assessed the effect of exogenous administered PYY3–36 on food intake in HF mice. HF mice remained sensitive to the anorectic effects of exogenous ip PYY3–36. Compared with low-fat-fed fed mice, the HF mice had lower endogenous plasma PYY and higher tissue PYY but similar PYY mRNA levels, suggesting a possible reduction of PYY release. Thus, fasting and postprandial endogenous plasma PYY levels were attenuated in obese humans and rodents. The PYY3–36 infusion study showed that the degree of plasma PYY reduction in obese subjects were likely associated with decreased satiety and relatively increased food intake. We conclude that obese subjects have a PYY deficiency that would reduce satiety and could thus reinforce their obesity.
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