76 research outputs found
Dietary fat quality impacts genome-wide DNA methylation patterns in a cross-sectional study of Greek preadolescents
4-hydroxynonenal causes impairment of human subcutaneous adipogenesis and induction of adipocyte insulin resistance
La fatty aldehyde dehydrogenase (régulation de son expression et rôle protecteur contre le stress oxydant dans l'action de l'insuline)
La voie de la Phosphatidylinositol 3-kinase (PI3K) régule l expression de nombreux gènes. Par une technique d analyse différentielle d expression, nous avons identifié des gènes dont l expression est régulée par la PI3K en réponse à l insuline dans des adipocytes isolés de rats. L un code pour la Fatty Aldehyde Dehydrogenase (FALDH), enzyme clé de la détoxification des aldéhydes issus de la peroxydation lipidique tels que l hydroxynonénal (HNE). Ces aldéhydes contribuent au stress oxydant associé au diabète de type 2. Dans un premier temps, nous avons caractérisé l expression du gène codant pour la FALDH et mis en évidence chez le rat après injection d insuline une augmentation de l expression de ce gène dans le foie et le tissu adipeux blanc. A l inverse, cette régulation par l insuline est perdue dans deux modèles de souris insulinorésistantes, ainsi que chez des rats traités à la steptozotocine, qui constituent un modèle hypoinsulinémique de type 1. Dans un deuxième temps, nous avons étudié les effets du stress oxydant sur la signalisation insulinique dans les adipocytes 3T3-L1. Nous avons montré une forte diminution des IRS-1 et IRS-2, et de la tyrosine phosphorylation associée, en présence de HNE. De plus, nous avons détecté une augmentation de la liaison covalente HNE/IRS-1. Aussi, les activités PI3K et PKB sont diminuées en présence de HNE, ce qui entraîne l altération de fonctions métaboliques contrôlées par l insuline. Nous avons montré ensuite que la FALDH restaure en partie la phosphorylation sur tyrosine d(IRS et les réponses métaboliques stimulées par l insuline, en présence de HNE suggérant que la LALDH améliore la signalisation insulinique dans les adipocytes 3T3-L1 soumis à un stress oxydant. En conclusion, notre étude a montré l implication des aldéhydes réactifs dans le développement de la résistance à l insuline, et le rôle protecteur que peut y jouer une enzyme de détoxification comme la FALDH dont l expression est contrôlée par l insuline.Phosphatidylinositol 3-kinase (PI3K) signalling regulates the expression of several genes. By employing RNA arbitrarily primed-PCR, we identified Fatty Aldehyde Dehydrogenase (FALDH) that is gene expression is regulated by PI3K in response to insulin in isolated rat adipocytes. FALDH is a key component of the detoxification pathway of aldehydes arising from lipid peroxidation events such as hydroxynomenal (HNE). Aldehydes induce oxidative stress associated with diabetes. Firstly, we have shown that FALDH mRNA expression increased in rat liver and white adipose tissue upon insulin injection. By contrast, FALDH m RNA expression was impaired in two models of insulin-resistant mice and in a hypoinsulinemic type 1 diabetes model of rats. Secondly, we analyzed the effect of oxidative stress on insulin signalling in 3T3-L1 adipocytes. We found that treatment with HNE leads to pronounced decrease in IRS proteins and their corresponding tyrosine phosphorylation. Moreover, we detected an increased covalent binding of HNE on IRS-1. PI3K and PKB activity are also down-regulated upon HNE treatment leading to the impairment of metabolic responses? Overexpression of FALDH partially restores tyrosine phosphorylation of IRS and metabolic response. This suggests that FALDH improves insulin signalling in adipocytes 3T3-L1 treated with HNE. To conclude, our study demonstrates the importance of reactive aldehydes in the development of insulin-resistance, and the role of detoxifying enzyme, such as FALDH, to protect cells.NICE-BU Sciences (060882101) / SudocSudocFranceF
Glucose- or insulin resistance-mediated β-cell replication: PKCζ integrates the proliferative signaling
Specific Glucose-Induced Control of Insulin Receptor Substrate-2 Expression Is Mediated via Ca 2+
Placental nutrient transporters adapt during persistent maternal hypoglycaemia in rats
Maternal malnutrition is associated with decreased nutrient transfer to the foetus, which may lead to foetal growth restriction, predisposing children to a variety of diseases. However, regulation of placental nutrient transfer during decreased nutrient availability is not fully understood. In the present study, the aim was to investigate changes in levels of placental nutrient transporters accompanying maternal hypoglycaemia following different durations and stages of gestation in rats. Maternal hypoglycaemia was induced by insulin-infusion throughout gestation until gestation day (GD)20 or until end of organogenesis (GD17), with sacrifice on GD17 or GD20. Protein levels of placental glucose transporters GLUT1 (45/55 kDa isotypes) and GLUT3, amino acid transporters SNAT1 and SNAT2, and insulin receptor (InsR) were assessed. On GD17, GLUT1-45, GLUT3, and SNAT1 levels were increased and InsR levels decreased versus controls. On GD20, following hypoglycaemia throughout gestation, GLUT3 levels were increased, GLUT1-55 showed the same trend. After cessation of hypoglycaemia at end of organogenesis, GLUT1-55, GLUT3, and InsR levels were increased versus controls, whereas SNAT1 levels were decreased. The increases in levels of placental nutrient transporters seen during maternal hypoglycaemia and hyperinsulinemia likely reflect an adaptive response to optimise foetal nutrient supply and development during limited availability of glucose
FoxO Feedback Control of Basal IRS-2 Expression in Pancreatic β-Cells Is Distinct From That in Hepatocytes
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