<i>KO</i> islets accumulate oxidative stress, inflammation, and fibrosis.

Abstract

<p>(A) mRNA-Seq expression values for 25/368 of the mRNAs identified by Venn analysis (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002277#pbio.1002277.g003" target="_blank">Fig 3C</a>; right panel, underlined) that are reduced by <i>Ire1α</i> because of glucose that accumulates in the <i>KO</i>^{<i>Fe/-; Cre</i>} ([<i>n</i> = 5], [<i>p</i>-values ≤ 0.05]). (B) Oxidized lipid (hydroxyl-octadecadienoic acids, HODEs) from islets of the indicated genotypes infected with <i>Ad-Cre Ad-GFP</i> or no virus control ([<i>n</i> = 2; controls versus <i>n</i> = 3; <i>Ad-Cre</i>], [<i>p</i> = 0.00434]). (C) Antinitrotyrosine immunohistochemistry (IHC) of islets from 8-mo-old <i>WT</i>^<i>Fe/Fe</i> and <i>KO</i>^{<i>Fe/Fe; Cre</i>} mice 15 wk post-Tam with or without BHA diet for 3 wk. (Scale bar, 50 μm) (<i>WT</i>^<i>Fe/Fe</i> [<i>n</i> = 4 with BHA], [<i>n</i> = 5 regular chow]), (<i>KO</i>^{<i>Fe/Fe; Cre</i>} [<i>n</i> = 5 with BHA], [<i>n</i> = 6 regular chow]). (<i>p</i> = 0.00698; <i>WT</i>^<i>Fe/Fe</i> versus <i>WT</i>^<i>Fe/Fe</i> with BHA), (<i>p</i> = 0.04018; <i>WT</i>^<i>Fe/Fe</i> versus <i>KO</i>^{<i>Fe/Fe; Cre</i>}) and (<i>p</i> = 0.04420; <i>KO</i>^{<i>Fe/Fe; Cre</i>} versus <i>KO</i>^{<i>Fe/Fe; Cre</i>} with BHA). (D) Masson’s trichrome stain (blue) for collagens. Results demonstrate increased staining surrounding <i>KO</i>^{<i>Fe/Fe; Cre</i>} islets with haemotoxylin (red) and eosin (black) co-stains. Quantification of percent strong collagen stain is shown below the images. Scale bar, 50 μm. (<i>WT</i>^<i>Fe/Fe</i> [<i>n</i> = 4 with BHA], [<i>n</i> = 5 regular chow]), (<i>KO</i>^{<i>Fe/Fe; Cre</i>} [<i>n</i> = 5 with BHA], [<i>n</i> = 6 without BHA]). Percent strong collagen stain significance for <i>WT</i>^<i>Fe/Fe</i> without BHA versus <i>KO</i>^{<i>Fe/Fe; Cre</i>} without BHA <i>p</i> = 0.01049). (E) 8-mo-old male mice carrying the doubly floxed allele (<i>Ire1α</i>^<i>Fe/Fe</i><i>)</i> with and without RIP-Cre 12 wk post-Tam had their pre-BHA GTTs taken, and then half were fed the antioxidant BHA supplemented chow diet for 3 wk or not before examining the mice by GTT again. (<i>WT</i>^<i>Fe/Fe</i> [<i>n</i> = 11 with BHA], [<i>n</i> = 12 regular chow], [<i>p</i> = 0.035]), (<i>KO</i>^{<i>Fe/Fe; Cre</i>} [<i>n</i> = 18 with BHA], [<i>n</i> = 16 without BHA], [<i>p</i> = 0.041]). <i>P</i>-values were calculated by one-tailed student’s <i>t</i> test comparison of the areas under the GTT curves for the biological replicates of control group <i>WT</i>^<i>Fe/Fe</i> versus the Tam-induced <i>KO</i>^{<i>Fe/Fe; Cre</i>} group.</p