Interleukin-6 increases the expression and activity of insulin-degrading enzyme

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOImpairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, respectively. In addition, during acute exercise, the inhibition of IL-6 prevented an increase in insulin clearance and IDE expression and activity, mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were significantly increased in plasma from humans, after an acute exercise, compared to pre-exercise values. Although the increase in plasma IDE activity was only marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 and IDE protein expression, was observed. Our outcomes indicate a novel function of IL-6 on the insulin metabolism expanding the possibilities for new potential therapeutic strategies, focused on insulin degradation, for the treatment and/or prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and act7112FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2014/24719-7; 2015/12611-

Thermal stress induces glycolytic beige fat formation via a myogenic state.

Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fibre-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evoke developmental plasticity remain incompletely understood. Here we report a type of beige adipocyte that has a critical role in chronic cold adaptation in the absence of β-adrenergic receptor signalling. This beige fat is distinct from conventional beige fat with respect to developmental origin and regulation, and displays enhanced glucose oxidation. We therefore refer to it as glycolytic beige fat. Mechanistically, we identify GA-binding protein α as a regulator of glycolytic beige adipocyte differentiation through a myogenic intermediate. Our study reveals a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cell that is required for energy homeostasis and survival

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9% and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15%), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3% and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3%) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.85586

BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.

Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health

Il primo master per coordinatori infermieristici di unit\ue0 operativa o dipartimento

Questo lavoro si propone di condividere l'esperienza dell'Universit\ue0 degli Studi di Milano- Facolt\ue0 di Medicina e Chirurgia- in merito al Master per Coordinatori infermieristici di Unit\ue0 Operativa e/o di Dipartimento, finanziati con FSE dell'A.A. 2003-2004. Nello specifico tale articolo vuole fotografare: - l'aspetto organizzativo: selezione per l'amissione, piano teorico formativo; - la metodologia utilizzata, consonna all'apprendimento degli adulti; - la qualit\ue0 percepita dai discenti

Benessere e ortoterapia: uno studio longitudinale con anziani in RSA

Introduzione. La letteratura ha mostrato che l\u2019ortoterapia rappresenta una fonte di benessere per gli anziani residenti in RSA, in cui il contatto con la natura genera benefici sul piano fisico, psicologico e sociale. A fronte del numero limitato di ricerche scientifiche sull\u2019argomento in Italia, la presente ricerca ha indagato l\u2019impatto dell\u2019ortoterapia sulla salute mentale e sulle opportunit\ue0 di esperienza ottimale degli anziani rispetto alla terapia occupazionale tradizionale. Metodi. Allo studio in crossover hanno partecipato 12 ospiti di una RSA milanese, suddivisi in due gruppi coinvolti in attivit\ue0 sia orticolturali sia occupazionali in due cicli successivi. Ciascun ciclo ha previsto sei incontri con cadenza settimanale. Ai partecipanti \ue8 stato somministrato Experience Sampling Method durante la settimana antecedente l\u2019avvio delle attivit\ue0 e al termine di ogni incontro al fine di rilevare in tempo reale la qualit\ue0 dell\u2019esperienza associata alla loro vita quotidiana e alle attivit\ue0 proposte. Inoltre, all\u2019inizio dello studio e alla fine di ciascun ciclo, i partecipanti hanno completato il Flow Questionnaire, la Mental Health Continuum Short Form e la Geriatric Depression Scale. Risultati. Le analisi hanno mostrato come sia le attivit\ue0 orticolturali che quelle occupazionali abbiano portato ad un incremento significativo del benessere dei partecipanti, nelle sue dimensioni psicologica ed emotiva. Le attivit\ue0 hanno rappresentato inoltre opportunit\ue0 in cui investire capacit\ue0 e risorse personali e da cui trarre esperienza ottimale. Conclusioni. I risultati suggeriscono che sia il coinvolgimento in attivit\ue0 complesse, pi\uf9 che l\u2019ortoterapia in s\ue9, a favorire il benessere dell\u2019anziano in RSA, sottolineando la necessit\ue0 di commisurare gli interventi agli interessi e ai vissuti dei destinatari

Overstress and Electrostatic Discharge in CMOS and BCD Integrated Circuits

The ESD qualification of the new technologies is obtained by testing different device structures an comparing the ESD robustness evaluated by means of different testing methods (HBM, MM, CDM and TLP). The influence of the layout parameters on the ESD robustness must also be characterized. In this paper we will present data concerning the ESD robustness of both 0.35 \u3bcm CMOS and 0.6 \u3bcm smart power (BCD5) protection structures. A study of the influence of layout parameters on the ESD robustness with different test methods (HBM, CDM and TLP) will be given. Failure analysis by means of electrical characterization, Emission Microscopy and SEM inspection will also been presented

Prevalence and severity of anaemia in patients with type 2 diabetic nephropathy and different degrees of chronic renal insufficiency

Background/Aim: Type 2 diabetes mellitus is the single most common cause of chronic kidney disease (CKD); however its real impact on renal anaemia has not been established. The aim of this study was to evaluate whether onset, severity, and prevalence of anaemia during the course of CKD is different between type 2 diabetic and non-diabetic patients. Methods: We enrolled 281 patients with: (1) type 2 diabetes and no CKD (n = 75); (2) type 2 diabetes plus CKD (n = 106), and (3) CKD without type 2 diabetes (n = 100). According to K/DOQI guidelines, the patients with renal insufficiency (i.e., those with a glomerular filtration rate < 60 ml/min) were subgrouped into three tertiles of CKD: (1) stage 3 (creatinine clearance 60-30 ml/min); (2) stage 4 (creatinine clearance 29-15 ml/min), and (3) stage 5 (creatinine clearance < 15 ml/min). Results: Anaemia was observed in 16% of the diabetic patients without CKD; it was more frequent in the diabetic patients with CKD than in the non-diabetic patients with CKD (61.7 vs. 52%, p < 0.05). The comparison among the tertiles showed that the prevalence of anaemia was significantly higher only in diabetic CKD patients of stages 4 and 5. The prevalence was higher in females independently of type 2 diabetes mellitus. In diabetics with a normal renal function, the haemoglobin levels were higher than in diabetics and non-diabetics with CKD, but the diabetics showed lower levels of haemoglobin than non-diabetics at stage 3 and stage 4 of CKD. Conclusions: Diabetic patients with CKD of stages 4 and 5 have a higher prevalence of anaemia than non-diabetic patients with comparable glomerular filtration rate. A higher awareness of this risk will allow earlier diagnosis and treatment. Copyright (c) 2007 S. Karger AG, Basel