Obesity is a growing problem in modern society and medicine. It closely associates with metabolic disorders such as type 2 diabetes mellitus (T2DM) and hepatic and cardiovascular diseases such as ...nonalcoholic fatty liver disease, atherosclerosis, myocarditis, and hypertension. Obesity is often associated with latent inflammation; however, the link between inflammation, obesity, T2DM, and cardiovascular diseases is still poorly understood. Insulin resistance is the earliest feature of metabolic disorders. It mostly develops as a result of dysregulated insulin signaling in insulin-sensitive cells, as compared to inactivating mutations in insulin receptor or signaling proteins that occur relatively rare. Here, we argue that inflammatory signaling provides a link between latent inflammation, obesity, insulin resistance, and metabolic disorders. We further hypothesize that insulin-activated PI3-kinase pathway and inflammatory signaling mediated by several IκB kinases may constitute negative feedback leading to insulin resistance at least in the fat tissue. Finally, we discuss perspectives for anti-inflammatory therapies in treating the metabolic diseases.
•Degree of insulin resistance correlated with amount of visceral fat, changes in incretin profile, and glucose metabolic parameters of 12 obese subjects with normal glucose tolerance (NGT) and 10 ...obese subjects having T2DM.•Basal activities of insulin cascade and mTOR were comparable in subcutaneous white adipose biopsies of NGT and T2DM individuals.•Phosphorylation of AS160 (Ser-318) was lower and phosphorylation of SGK1 (Ser-422) was higher in T2DM vs. NGT fat biopsies.•Changes in phosphorylation of AS160 and SGK1 correlate with insulin resistance, changes in incretin profile, and T2DM.
To compare basal insulin and mTOR signaling in subcutaneous fat of obese T2DM vs. obese subjects with normal glucose tolerance (NGT), and correlate it with clinical parameters of carbohydrate metabolism and incretin secretion profiles.
Recruited were 22 patients with long (>10 years) and morbid (BMI > 35 kg/m2) obesity, 12 of which had NGT and 10 had T2DM. Hyperinsulinemic-euglycemic clamp test and HOMA-IR were used to measure insulin resistance. Blood samples taken at 0, 30 and 120 min of food load test were used to assess incretin profile, insulin and glucose levels. Amount of total and visceral fat was determined by bioelectrical impedance analysis. Subcutaneous fat biopsies were obtained during bariatric surgery for all patients and analyzed by western blots.
As assessed by western blots of insulin receptor substrate (IRS), Akt, Raptor, Rictor, mTOR and S6K1, the basal insulin signaling and mTORC activities were comparable in NGT and T2DM groups, whereas phosphorylation of AS160 was significantly lower and that of serum and glucocorticoid-induced kinase (SGK) was significantly higher in T2DM group. Various correlations were found between the degree of insulin resistance and amount of visceral fat, changes in incretin profile, glucose metabolic parameters and phosphorylation level of AS160, incretin secretion profile and phosphorylated levels of AS160 or SGK1.
Altered phosphorylation of AS160 and SGK1 is associated with obese T2DM phenotype.
Obesity is a major risk factor for type 2 diabetes and metabolic syndrome and an essential medical and social problem. In the first part of the review, we briefly highlight the biochemical basis of ...metabolic disbalance in obesity and evolution of our views on the mechanisms of insulin resistance development in insulin-sensitive tissues. Because obesity relates to the disturbance in the normal physiology of fat tissue, the second part of the review focuses on latent inflammation that develops in obesity and is supported by immune cells. Finally, the problem of adipocyte hypertrophy, reduced regenerative potential of fat progenitor cells, and impaired renewal of fat depots is discussed in the context of type 2 diabetes pathogenesis.
In this paper, a technique for high-density BaZr1-xYxO3-6(x=0÷0.15) ceramics producing without the use of sintering additives is discussed. The obtained perovskite-like oxides are single-phase at the ...yttrium concentration of x=0÷0.1. For single-phase compounds, the lattice parameter increases when the yttrium addition rises. The microstructure of the produced samples was studied by scanning electron microscopy. Measurements of the thermal expansion and the total conductivity of BaZr1-xYxO3-8materials at different humidity evidence about the absence of phase transitions. The values of the specific conductivity depending on the temperature, the concentration of the acceptor impurity as well as the composition of the gas phase were implemented by the DC 4-probe method. In addition, the dependences of the effective activation energies on the conditions listed above are shown.
In this work, the effect of the content of CuO, ZnO, Al2O3, NiO, Fe2O3, Co3O4 and MoO3 additives on the sinterability, microstructure, and electrical properties of La0.9Sr0.1ScO3-α proton-conducting ...oxide in a form of tubes produced by slip casting is studied. It is shown that the relative density of La0.9Sr0.1ScO3-α tubes without sintering aids is ~86%. The introduction of 1.0 wt % ZnO, Al2O3, NiO or 0.5 ÷ 1.0 wt % Co3O4 leads to a relative density of ceramics higher than 95%. Among dense ceramic tubes, LSS +0.5 wt % Co3O4 has the highest electrical conductivity. The introduction of 1 wt % Fe2O3 additive does not affect the sinterability of the LSS, and 1 wt % CuO and MoO3 inhibits LSS sintering. Single protonic ceramic fuel cells based on LSS +0.5 wt % Co3O4 and LSS +1.0 wt % NiO supporting electrolyte tubes with a thickness of 300 μm are studied. The maximum power density of about 30 mW/cm2 at 800 °C was obtained for a cell based on LSS +0.5 wt % Co3O4 using wet hydrogen as fuel and air as an oxidizing gas.
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•Co3O4 recognized to be the best sintering additive for La0.9Sr0.1ScO3-δ electrolyte.•The way of sintering additive introduction affects microstructure in case of Co3O4.•The optimal amount of Co3O4 additive was found to be 0.5 wt%.•Highly dense ceramic tubes of proton-conducting electrolyte were obtained.
This review focuses on basic principles of motility in different cell types, formation of the specific cell structures that enable directed migration, and how external signals are transduced into ...cells and coupled to the motile machinery. Feedback mechanisms and their potential role in maintenance of internal chemotactic gradients and persistence of directed migration are highlighted.
Nanosized (
d
∼70 nm) particles of metal-organic framework (MOF) based on zirconium and 2-aminoterephthalic acid, NH
2
-UiO-66, were prepared by a simple one-pot method. Due to the small particle ...size, the presence of amino groups, low toxicity, and high sorption capacity caused by large pore size, the obtained MOF is a perfect platform for the preparation of combined cytostatic agents with prolonged action. Nano-MOF is highly stable in distilled water, which allows for the sorption of a cytostatic drug without crystal destruction. The MOF gradually loses crystallinity in phosphate-buffered saline (pH 7.4), resulting in a gradual release of the drug under near-physiological conditions. Sorption studies have shown that approximately 50% of the drug is adsorbed after 48 h of storage of NH
2
-UiO-66 in a doxorubicin solution. To demonstrate the prolonged cytostatic effect, cytotoxicity was studied for different incubation times (8, 24, and 48 h) against two cell cultures, MRC-5 (fibroblasts, healthy cells) and Hep-2 (human laryngeal cancer cells). Doxorubicin-doped nano-MOF shows the highest toxicity, which increases with increasing incubation time, thus confirming prolonged cytostatic effect.
—
Ceramic Sr
2
Ce
0.95
Yb
0.05
О
4
samples have been synthesized by the Pechini process and their electrical conductivity has been determined as a function of temperature (300–900°C),
and
(40–2500 ...Pa) using four-probe and impedance measurements. In air at high temperatures, the material is a mixed oxygen–hole conductor, with predominantly oxygen-ion conductivity. At reduced temperatures, proton conductivity prevails, with σ ~
Abstract
In this paper, a technique for high-density BaZr
1-x
Y
x
O
3-6
(x=0÷0.15) ceramics producing without the use of sintering additives is discussed. The obtained perovskite-like oxides are ...single-phase at the yttrium concentration of x=0÷0.1. For single-phase compounds, the lattice parameter increases when the yttrium addition rises. The microstructure of the produced samples was studied by scanning electron microscopy. Measurements of the thermal expansion and the total conductivity of BaZr
1-x
Y
x
O
3-8
materials at different humidity evidence about the absence of phase transitions. The values of the specific conductivity depending on the temperature, the concentration of the acceptor impurity as well as the composition of the gas phase were implemented by the DC 4-probe method. In addition, the dependences of the effective activation energies on the conditions listed above are shown.
Obesity and latent inflammation in adipose tissue significantly contribute to the development of insulin resistance (IR) and type 2 diabetes. Here we studied whether the antiinflammatory ...interleukin-4 (IL-4) can restore insulin sensitivity in cultured 3T3-L1 adipocytes. The activity of key components of the insulin signaling cascade was assessed by immunoblotting using phospho-specific antibodies to insulin receptor substrate IRS1 (Tyr612), Akt (Thr308 and Ser473), and AS160 (Ser318) protein that regulates translocation of the
GLUT4
glucose transporter to the plasma membrane. IR was induced in mature adipocytes with albumin-conjugated palmitate. IR significantly reduced phosphorylation levels of all the above-mentioned proteins. Addition of IL-4 to the culturing medium during IR induction led to a dose-dependent stimulation of the insulin-promoted phosphorylation of IRS1, Akt, and AS160. At the optimal concentration of 50 ng/ml, IL-4 fully restored activation of the insulin cascade in IR cells, but it did not affect insulin signaling activation in the control cells. IL- 4 neither upregulated expression of key adipogenesis markers
GLUT4
and
PPARγ
nor caused lipid accumulation in the adipocytes. These results demonstrate that IL-4 can restore insulin sensitivity in adipocytes via mechanisms not associated with induced adipogenesis or
de novo
formation of lipid depots.
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