(Re)generating human beta cells : status, pitfalls, and perspectives

Diabetes mellitus results from disturbed glucose homeostasis due to an absolute (type 1) or relative (type 2) deficiency of insulin, a peptide hormone almost exclusively produced by the beta cells of the endocrine pancreas in a tightly regulated manner. Current therapy only delays disease progression through insulin injection and/or oral medications that increase insulin secretion or sensitivity, decrease hepatic glucose production, or promote glucosuria. These drugs have turned diabetes into a chronic disease as they do not solve the underlying beta cell defects or entirely prevent the long-term complications of hyperglycemia. Beta cell replacement through islet transplantation is a more physiological therapeutic alternative but is severely hampered by donor shortage and immune rejection. A curative strategy should combine newer approaches to immunomodulation with beta cell replacement. Success of this approach depends on the development of practical methods for generating beta cells, either in vitro or in situ through beta cell replication or beta cell differentiation. This review provides an overview of human beta cell generation

HS 2325+8205 - an ideal laboratory for accretion disk physics

We identify HS 2325+8205 as an eclipsing, frequently outbursting dwarf nova with an orbital period of 279.841731(5) min. Spectroscopic observations are used to derive the radial velocity curve of the secondary star from absorption features and also from the H-alpha emission lines, originating from the accretion disc, yielding K_secondary = K_abs = 237 +- 28 km/s and K_emn = 145 +- 9 km/s respectively. The distance to the system is calculated to be 400 (+200, -140) pc. A photometric monitoring campaign reveals an outburst recurrence time of 12-14 d, The combination of magnitude range (17-14 mag), high declination, eclipsing nature and frequency of outbursts makes HS 2325+8205 the ideal system for "real-time" studies of the accretion disc evolution and behavior in dwarf nova outbursts.Comment: 20 pages, 7 figures. Accepted for Publications of the Astronomical Society of the Pacifi

IPHAS J062746.41+014811.3: a deeply eclipsing intermediate polar

We present time-resolved photometry of a cataclysmic variable discovered in the Isaac Newton Telescope Photometric Halpha Survey of the northern galactic plane, IPHAS J062746.41+014811.3 and classify the system as the fourth deeply eclipsing intermediate polar known with an orbital period of Porb=8.16 h, and spin period of Pspin=2210 s. The system shows mild variations of its brightness, that appear to be accompanied by a change in the amplitude of the spin modulation at optical wavelengths, and a change in the morphology of the eclipse profile. The inferred magnetic moment of the white dwarf is mu_wd = 6-7 x 10^33 Gcm^3, and in this case IPHAS J0627 will either evolve into a short-period EX Hya-like intermediate polar with a large Pspin\Porb ratio, or, perhaps more likely, into a synchronised polar. Swift observations show that the system is an ultraviolet and X-ray source, with a hard X-ray spectrum that is consistent with those seen in other intermediate polars. The ultraviolet light curve shows orbital modulation and an eclipse, while the low signal-to-noise ratio X-ray light curve does not show a significant modulation on the spin period. The measured X-ray flux is about an order of magnitude lower than would be expected from scaling by the optical fluxes of well-known X-ray selected intermediate polars.Comment: 34 pages, 9 figures, accepted for publication in Ap

Peroxisome proliferator-activated receptor (PPAR) agonists decrease lipoprotein lipase secretion and glycated LDL uptake by human macrophages

AbstractLipoprotein lipase (LPL) acts independently of its function as triglyceride hydrolase by stimulating macrophage binding and uptake of native, oxidized and glycated LDL. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors expressed in monocyte/macrophages, where they control cholesterol homeostasis. Here we study the role of PPARs in the regulation of LPL expression and activity in human monocytes and macrophages. Incubation of human monocytes or macrophages with PPARα or PPARγ ligands increases LPL mRNA and intracellular protein levels. By contrast, PPAR activators decrease secreted LPL mass and enzyme activity in differentiated macrophages. These actions of PPAR activators are associated with a reduced uptake of glycated LDL and could influence atherosclerosis development associated with diabetes

Farnesoid X Receptor Deficiency Improves Glucose Homeostasis in Mouse Models of Obesity

International audienceOBJECTIVE Bile acids (BA) participate in the maintenance of metabolic homeostasis acting through different signaling pathways. The nuclear BA receptor farnesoid X receptor (FXR) regulates pathways in BA, lipid, glucose, and energy metabolism, which become dysregulated in obesity. However, the role of FXR in obesity and associated complications, such as dyslipidemia and insulin resistance, has not been directly assessed. RESEARCH DESIGN AND METHODS Here, we evaluate the consequences of FXR deficiency on body weight development, lipid metabolism, and insulin resistance in murine models of genetic and diet-induced obesity. RESULTS FXR deficiency attenuated body weight gain and reduced adipose tissue mass in both models. Surprisingly, glucose homeostasis improved as a result of an enhanced glucose clearance and adipose tissue insulin sensitivity. In contrast, hepatic insulin sensitivity did not change, and liver steatosis aggravated as a result of the repression of β-oxidation genes. In agreement, liver-specific FXR deficiency did not protect from diet-induced obesity and insulin resistance, indicating a role for nonhepatic FXR in the control of glucose homeostasis in obesity. Decreasing elevated plasma BA concentrations in obese FXR-deficient mice by administration of the BA sequestrant colesevelam improved glucose homeostasis in a FXR-dependent manner, indicating that the observed improvements by FXR deficiency are not a result of indirect effects of altered BA metabolism. CONCLUSIONS Overall, FXR deficiency in obesity beneficially affects body weight development and glucose homeostasis

The 2022–2023 accretion outburst of the young star V1741 Sgr

© 2024 The Author(s). Published by Oxford University Press on behalf of Royal Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/V1741 Sgr (= SPICY 71482/Gaia22dtk) is a Classical T Tauri star on the outskirts of the Lagoon Nebula. After at least a decade of stability, in mid-2022, the optical source brightened by ∼3 mag over 2 months, remained bright until early 2023, then dimmed erratically over the next 4 months. This event was monitored with optical and infrared spectroscopy and photometry. Spectra from the peak (October 2022) indicate an EX Lup-type (EXor) accretion outburst, with strong emission from H I, He I, and Ca II lines and CO bands. At this stage, spectroscopic absorption features indicated a temperature of T ∼ 4750 K with low-gravity lines (e.g. Ba II and Sr II). By April 2023, with the outburst beginning to dim, strong TiO absorption appeared, indicating a cooler T ∼ 3600 K temperature. However, once the source had returned to its pre-outburst flux in August 2023, the TiO absorption and the CO emission disappeared. When the star went into outburst, the source’s spectral energy distribution became flatter, leading to bluer colours at wavelengths shorter than ∼1.6 m and redder colours at longer wavelengths. The brightening requires a continuum emitting area larger than the stellar surface, likely from optically thick circumstellar gas with cooler surface layers producing the absorption features. Additional contributions to the outburst spectrum may include blue excess from hotspots on the stellar surface, emission lines from diffuse gas, and reprocessed emission from the dust disc. Cooling of the circumstellar gas would explain the appearance of TiO, which subsequently disappeared once this gas had faded and the stellar spectrum reemerged.Peer reviewe

Rev-erb-alpha modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy

The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and the inflammatory response in macrophages. We show here that Rev-erb-α is highly expressed in oxidative skeletal muscle and plays a role in mitochondrial biogenesis and oxidative function, in gain- and loss-of function studies. Rev-erb-α-deficiency in skeletal muscle leads to reduced mitochondrial content and oxidative function, resulting in compromised exercise capacity. This phenotype was recapitulated in isolated fibers and in muscle cells upon Rev-erbα knock-down, while Rev-erb-α over-expression increased the number of mitochondria with improved respiratory capacity. Rev-erb-α-deficiency resulted in deactivation of the Stk11–Ampk–Sirt1–Ppargc1-α signaling pathway, whereas autophagy was up-regulated, resulting in both impaired mitochondrial biogenesis and increased clearance. Muscle over-expression or pharmacological activation of Rev-erb-α increased respiration and exercise capacity. This study identifies Rev-erb-α as a pharmacological target which improves muscle oxidative function by modulating gene networks controlling mitochondrial number and function

SDSS J162520.29+120308.7 – a new SU Ursae Majoris star in the period gap

We report results of an extensive world-wide observing campaign devoted to the recently discovered dwarf nova SDSS J162520.29+120308.7 (SDSS J1625). The data were obtained during the July 2010 eruption of the star and in August and September 2010 when the object was in quiescence. During the July 2010 superoutburst, SDSS J1625 clearly displayed superhumps with a mean period of Psh = 0.095942(17) days (138.16 ± 0.02 min) and a maximum amplitude reaching almost 0.4 mag. The superhump period was not stable, decreasing very rapidly at a rate of ˙P = −1.63(14) × 10−3 at the beginning of the superoutburst and increasing at a rate of ˙P = 2.81(20) × 10−4 in the middle phase. At the end of the superoutburst, it stabilized around the value of Psh = 0.09531(5) day. During the first twelve hours of the superoutburst, a low-amplitude double wave modulation was observed whose properties are almost identical to early superhumps observed in WZ Sge stars. The period of early superhumps, the period of modulations observed temporarily in quiescence, and the period derived from radial velocity variations are the same within measurement errors, allowing us to estimate the most probable orbital period of the binary to be Porb = 0.09111(15) days (131.20 ± 0.22 min). This value clearly indicates that SDSS J1625 is another dwarf nova in the period gap. Knowledge of the orbital and superhump periods allows us to estimate the mass ratio of the system to be q ≈ 0.25. This high value poses serious problems for both the thermal and tidal instability (TTI) model describing the behaviour of dwarf novae and for some models explaining the origin of early superhumps