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• W1990544892 abstract "High-density lipoproteins (HDLs) protect pancreatic β-cells against apoptosis. This property might relate to the increased risk to develop diabetes in patients with low HDL blood levels. However, the mechanisms by which HDLs protect β-cells are poorly characterized. Here we used a transcriptomic approach to identify genes differentially modulated by HDLs in β-cells subjected to apoptotic stimuli. The transcript encoding 4E-binding protein (4E-BP)1 was up-regulated by serum starvation, and HDLs blocked this increase. 4E-BP1 inhibits cap-dependent translation in its non- or hypophosphorylated state but it loses this ability when hyperphosphorylated. At the protein level, 4E-BP1 was also up-regulated in response to starvation and IL-1β, and this was blunted by HDLs. Whereas an ectopic increase of 4E-BP1 expression induced β-cell death, silencing 4E-BP1 increase with short hairpin RNAs inhibited the apoptotic-inducing capacities of starvation. HDLs can therefore protect β-cells by blocking 4E-BP1 protein expression, but this is not the sole protective mechanism activated by HDLs. Indeed, HDLs blocked apoptosis induced by endoplasmic reticulum stress with no associated decrease in total 4E-BP1 induction. Although, HDLs favored the phosphorylation, and hence the inactivation of 4E-BP1 in these conditions, this appeared not to be required for HDL protection. Our results indicate that HDLs can protect β-cells through modulation of 4E-BP1 depending on the type of stress stimuli." @default.
• W1990544892 created "2016-06-24" @default.
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• W1990544892 date "2009-10-01" @default.
• W1990544892 modified "2023-10-15" @default.
• W1990544892 title "Involvement of 4E-BP1 in the Protection Induced by HDLs on Pancreatic β-Cells" @default.
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• W1990544892 doi "https://doi.org/10.1210/me.2008-0448" @default.
• W1990544892 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5419142" @default.
• W1990544892 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19574449" @default.
• W1990544892 hasPublicationYear "2009" @default.
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