2,081 research outputs found
Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation
We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistance via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the long-chain fatty acid oleate (150 nmol/min, 24 h), the medium-chain fatty acid caprylate, or the solvent. Corticosterone (Cort) and norepinephrine (NE) were measured as indexes for HPA axis and sympathetic activity, respectively. Insulin sensitivity was assessed by means of an intravenous glucose tolerance test (IVGTT). Oleate infusion induced increases in plasma Cort (Δ = 13.5 ± 3.6 µg/dl; P < 0.05) and NE (Δ = 235 ± 76 ng/l; P < 0.05), whereas caprylate and solvent had no effect. The area under the insulin response curve to the IVGTT was larger in the oleate-treated group than in the caprylate and solvent groups (area = 220 ± 35 vs. 112 ± 13 and 106 ± 8, respectively, P < 0.05). The area under the glucose response curves was comparable [area = 121 ± 13 (oleate) vs. 135 ± 20 (caprylate) and 96 ± 11 (solvent)]. The results are consistent with the concept that increased portal free fatty acid is involved in the induction of visceral obesity-related insulin resistance via activation of the HPA axis and sympathetic system.
General Non-equilibrium Theory of Colloid Dynamics
A non-equilibrium extension of Onsager's canonical theory of thermal
fluctuations is employed to derive a self-consistent theory for the description
of the statistical properties of the instantaneous local concentration profile
n(r,t) of a colloidal liquid in terms of the coupled time evolution equations
of its mean value n(r,t) and of the covariance {\sigma}(r,r';t) \equiv
of its fluctuations {\delta}n(r, t) = n(r, t) -
n(r, t). These two coarse-grained equations involve a local mobility function
b(r, t) which, in its turn, is written in terms of the memory function of the
two-time correlation function C(r, r' ; t, t') \equiv <{\delta}n(r,
t){\delta}n(r',t')>. For given effective interactions between colloidal
particles and applied external fields, the resulting self-consistent theory is
aimed at describing the evolution of a strongly correlated colloidal liquid
from an initial state with arbitrary mean and covariance n^0(r) and
{\sigma}^0(r,r') towards its equilibrium state characterized by the equilibrium
local concentration profile n^(eq)(r) and equilibrium covariance
{\sigma}^(eq)(r,r').
This theory also provides a general theoretical framework to describe
irreversible processes associated with dynamic arrest transitions, such as
aging, and the effects of spatial heterogeneities
Possible experiment to check the reality of a nonequilibrium temperature
An experiment is proposed to check the physical reality of a nonequilibrium absolute temperature previously proposed from theoretical grounds in the framework of extended irreversible thermodynamics
Some thoughts about nonequilibrium temperature
The main objective of this paper is to show that, within the present
framework of the kinetic theoretical approach to irreversible thermodynamics,
there is no evidence that provides a basis to modify the ordinary Fourier
equation relating the heat flux in a non-equilibrium steady state to the
gradient of the local equilibrium temperature. This fact is supported, among
other arguments, through the kinetic foundations of generalized hydrodynamics.
Some attempts have been recently proposed asserting that, in the presence of
non-linearities of the state variables, such a temperature should be replaced
by the non-equilibrium temperature as defined in Extended Irreversible
Thermodynamics. In the approximations used for such a temperature there is so
far no evidence that sustains this proposal.Comment: 13 pages, TeX, no figures, to appear in Mol. Phy
Mdm2 Induces Mono-Ubiquitination of FOXO4
Background: The Forkhead box O (FOXO) class of transcription factors are involved in the regulation of several cellular responses including cell cycle progression and apoptosis. Furthermore, in model organisms FOXOs act as tumor suppressors and affect aging. Previously, we noted that FOXOs and p53 are remarkably similar within their spectrum of regulatory proteins [1]. For example, the de-ubiquitinating enzyme USP7 removes ubiquitin from both FOXO and p53. However, Skp2 has been identified as E3 ligase for FOXO1, whereas Mdm2 is the prime E3 ligase for p53. Principal Findings/Methodology: Here we provide evidence that Mdm2 acts as an E3 ligase for FOXO as well. In vitro incubation of Mdm2 and FOXO results in ATP-dependent (multi)mono-ubiquitination of FOXO similar to p53. Furthermore, in vivo co-expression of Mdm2 and FOXO induces FOXO mono-ubiquitination and consistent with this result, siRNAmediated depletion of Mdm2 inhibits mono-ubiquitination of FOXO induced by hydrogen peroxide. Regulation of FOXO ubiquitination by Mdm2 is likely to be direct since Mdm2 and FOXO co-immunoprecipitate. In addition, Mdm2-mediated ubiquitination regulates FOXO transcriptional activity. Conclusions/Significance: These data identify Mdm2 as a novel E3 ligase for FOXOs and extend the analogous mode o
Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr 3]octreotate
Introduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included fo
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