5,445 research outputs found

    Plasma kisspeptin levels are associated with insulin secretion in nondiabetic individuals

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    To evaluate if plasma kisspeptin concentrations are associated with insulin secretion, as suggested by recent in vitro studies, independently of confounders. 261 nondiabetic subjects were stratified into tertiles according to kisspeptin values. Insulin secretion was assessed using indexes derived from oral glucose tolerance test (OGTT). After adjusting for age, gender, and BMI, subjects in the highest (tertile 3) kisspeptin group exhibited significantly lower values of insulinogenic index, corrected insulin response (CIR30), and Stumvoll indexes for first-phase and second-phase insulin release as compared with low (tertile 1) or intermediate (tertile 2) kisspeptin groups. Univariate correlations between kisspeptin concentration and metabolic variables showed that kisspeptin concentration was significantly and positively correlated with age, blood pressure, and 2-h post-load glucose, and inversely correlated with BMI, and waist circumference. There was an inverse relationship between kisspeptin levels and OGTT-derived indexes of glucose-stimulated insulin secretion. A multivariable regression analysis in a model including all the variables significantly correlated with kisspeptin concentration showed thar age (β = -0.338, P<0.0001), BMI (β = 0.272, P<0.0001), 2-h post-load glucose (β = -0.229, P<0.0001), and kisspeptin (β = -0.105, P = 0.03) remained associated with insulinogenic index. These factors explained 34.6% of the variance of the insulinogenic index. In conclusion, kisspeptin concentrations are associated with insulin secretion independently of important determinants of glucose homeostasis such as gender, age, adiposity, 2-h post-load glucose, and insulin sensitivity

    3D climate modeling of close-in land planets: Circulation patterns, climate moist bistability and habitability

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    The inner edge of the classical habitable zone is often defined by the critical flux needed to trigger the runaway greenhouse instability. This 1D notion of a critical flux, however, may not be so relevant for inhomogeneously irradiated planets, or when the water content is limited (land planets). Here, based on results from our 3D global climate model, we find that the circulation pattern can shift from super-rotation to stellar/anti stellar circulation when the equatorial Rossby deformation radius significantly exceeds the planetary radius. Using analytical and numerical arguments, we also demonstrate the presence of systematic biases between mean surface temperatures or temperature profiles predicted from either 1D or 3D simulations. Including a complete modeling of the water cycle, we further demonstrate that for land planets closer than the inner edge of the classical habitable zone, two stable climate regimes can exist. One is the classical runaway state, and the other is a collapsed state where water is captured in permanent cold traps. We identify this "moist" bistability as the result of a competition between the greenhouse effect of water vapor and its condensation. We also present synthetic spectra showing the observable signature of these two states. Taking the example of two prototype planets in this regime, namely Gl581c and HD85512b, we argue that they could accumulate a significant amount of water ice at their surface. If such a thick ice cap is present, gravity driven ice flows and geothermal flux should come into play to produce long-lived liquid water at the edge and/or bottom of the ice cap. Consequently, the habitability of planets at smaller orbital distance than the inner edge of the classical habitable zone cannot be ruled out. Transiting planets in this regime represent promising targets for upcoming observatories like EChO and JWST.Comment: Accepted for publication in Astronomy and Astrophysics, complete abstract in the pdf, 18 pages, 18 figure

    Insulin-like growth factor-1 is a negative modulator of glucagon secretion

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    Glucagon secretion involves a combination of paracrine, autocrine, hormonal, and autonomic neural mechanisms. Type 2 diabetes often presents impaired glucagon suppression by insulin and glucose. Insulin-like growth factor-I (IGF-1) has elevated homology with insulin, and regulates pancreatic β-cells insulin secretion. Insulin and IGF-1 receptors share considerable structure homology and function. We hypothesized the existence of a mechanism linking the inhibition of α-cells glucagon secretion to IGF-1. Herein, we evaluated the association between plasma IGF-1 and glucagon levels in 116 nondiabetic adults. After adjusting for age gender and BMI, fasting glucagon levels were positively correlated with 2-h post-load glycaemia, HOMA index and fasting insulin, and were negatively correlated with IGF-1 levels. In a multivariable regression, the variables independently associated to fasting glucagon were circulating IGF-1 levels, HOMA index and BMI, explaining 20.7% variation. To unravel the molecular mechanisms beneath IGF-1 and glucagon association, we investigated whether IGF-1 directly modulates glucagon expression and secretion in an in vitro model of α-cells. Our data showed that IGF-1 inhibits the ability of low glucose concentration to stimulate glucagon expression and secretion via activation of the phosphatidylinositol-3-kinase/Akt/FoxO1 pathway. Collectively, our results suggest a new regulatory role of IGF-1 on α-cells biological function

    Effect of vasopressin 1b receptor blockade on the hypothalamic-pituitary-adrenal response of chronically stressed rats to a heterotypic stressor

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    Exposure to chronic restraint (CR) modifies the hypothalamic–pituitary–adrenal (HPA) axis response to subsequent acute stressors with adaptation of the response to a homotypic and sensitization of the response to a heterotypic stressor. Since vasopressin (AVP) activity has been reported to change during chronic stress, we investigated whether this was an important factor in HPA facilitation. We therefore tested whether vasopressin 1b receptor (AVPR1B) blockade altered the ACTH and corticosterone response to heterotypic stressors following CR stress. Adult male rats were exposed to CR, single restraint, or were left undisturbed in the home cage. Twenty-four hours after the last restraint, rats were injected with either a AVPR1B antagonist (Org, 30 mg/kg, s.c.) or vehicle (5% mulgofen in saline, 0.2/kg, s.c.) and then exposed to either restraint, lipopolysaccharide (LPS) or white noise. CR resulted in the adaptation of the ACTH and corticosterone response to restraint and this effect was not prevented by pretreatment with Org. Although we found no effect of CR on LPS-induced ACTH and corticosterone secretion, both repeated and single episodes of restraint induced the sensitization of the ACTH, but not corticosterone response to acute noise. Pretreatment with Org reduced the exaggerated ACTH response to noise after both single and repeated exposure to restraint

    Characterization of multilayer stack parameters from X-ray reflectivity data using the PPM program: measurements and comparison with TEM results

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    Future hard (10 -100 keV) X-ray telescopes (SIMBOL-X, Con-X, HEXIT-SAT, XEUS) will implement focusing optics with multilayer coatings: in view of the production of these optics we are exploring several deposition techniques for the reflective coatings. In order to evaluate the achievable optical performance X-Ray Reflectivity (XRR) measurements are performed, which are powerful tools for the in-depth characterization of multilayer properties (roughness, thickness and density distribution). An exact extraction of the stack parameters is however difficult because the XRR scans depend on them in a complex way. The PPM code, developed at ERSF in the past years, is able to derive the layer-by-layer properties of multilayer structures from semi-automatic XRR scan fittings by means of a global minimization procedure in the parameters space. In this work we will present the PPM modeling of some multilayer stacks (Pt/C and Ni/C) deposited by simple e-beam evaporation. Moreover, in order to verify the predictions of PPM, the obtained results are compared with TEM profiles taken on the same set of samples. As we will show, PPM results are in good agreement with the TEM findings. In addition, we show that the accurate fitting returns a physically correct evaluation of the variation of layers thickness through the stack, whereas the thickness trend derived from TEM profiles can be altered by the superposition of roughness profiles in the sample image
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