Transcriptomic and Functional Analyses on the Effects of Dioxin on Insulin Secretion of Pancreatic Islets and β‑Cells

In this study, transcriptomic and Ingenuity Pathway Analysis (IPA) underlined that an ex-vivo TCDD treatment (0.1 nM) stimulated insulin-release in mouse pancreatic islets via the effect on the Akt-mTOR-p70S6K, AMPK and ERK1/2 pathways. Functional studies using both ex-vivo islets and the mouse β-cell-line (Min-6) validated the stimulatory effects of TCDD (0.1 and 1 nM) on basal-insulin secretion. At 0.1 nM TCDD treatment on Min-6, Western blot analysis showed activation of ERK1/2 and decreased expression of pyruvate dehydrogenase kinase (PDK). A reduction of PDK expression is associated with an increase of pyruvate dehydrogenase flux. This observation was supported by the detection of significantly higher cellular ATP levels, an increase of glucose-stimulated-insulin-secretion (GSIS), and an inhibition of the AMPK pathway. At 1 nM TCDD treatment on Min-6, significant inhibitions of the Akt-mTOR pathway, cellular ATP production, and GSIS were evident. The experimental studies in Min-6 supported the IPA of transcriptomic data in pancreatic islets. Collectively, TCDD treatment caused an elevated basal-insulin release in both islets and β-cell cultures. Moreover, our data revealed that the modulation of the Akt-mTOR-p70S6K, AMPK and ERK1/2 pathways might be an important component of the mechanism for the TCDD-perturbing effects on ATP production in β-cells in affecting insulin secretion

T_tridentatus_genome_contigs.fa

T_tridentatus genome contigs assembled as described in accompanying manuscript. NB .fasta.gz file, needs to be unpacked using gzip or similar before us

C_rotundicauda_chelicerate_transcriptome

C_rotundicauda chelicerate transcriptome assembled using Trinity as described in accompanying manuscript. .fasta.gz file, needs unpacking using gzip or similar before us

The median expression of genes in each paired samples.

<p>The median expression of genes in each paired samples.</p

Unsupervised clustering of all gene expression in 9 paired samples, 3 with recurrent implantation failure (RIF), 3 with recurrent miscarriage (RM), and 3 fertile controls (C).

<p>Unsupervised clustering of all gene expression in 9 paired samples, 3 with recurrent implantation failure (RIF), 3 with recurrent miscarriage (RM), and 3 fertile controls (C).</p

Scattered plots showed positive correlation of transcriptome in paired samples of each subjects.

<p>RIF: recurrent implantation failure; RM: recurrent miscarriage; C: fertile control.</p

Histogram showing the coefficients of Spearman's rank correlation in different groups.

<p>Results shown were mean ± SE. *t test p = 0.027; SE: standard error; RIF: recurrent implantation failure; RM: recurrent miscarriage; C: fertile control.</p

L_polyphemus_genome_contigs.fa

L polyphemus genome contigs assembled as described in accompanying manuscript. NB .fasta.gz file, needs to be unpacked using gzip or similar before us

T_tridentatus_chelicerate_transcriptome

T. tridentatus chelicerate transcriptome assembled using Trinity as described in accompanying manuscript. .fasta.gz file, needs unzipping using gzip or similar before use

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

24 mai 19431943/05/24 (A44,N15431)