Short term exposure of beta cells to low concentrations of interleukin-1ß improves insulin secretion through focal adhesion and actin remodeling and regulation of gene expression

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Arous, C (Author) Other; Ferreira, PG (Author) Other; Dermitzakis, ET (Author) Other; Halban, PA (Author) Other

Journal

Title: Journal of Biological Chemistry

Vol. 290

Pages: 6653-6669

ISSN: 0021-9258

Publisher: Elsevier

Indexing

Scopus - 20 Citations

Scientific classification

CORDIS: Natural sciences > Biological sciences > Biology > Molecular biology ; Natural sciences > Biological sciences > Biology > Computational biology

FOS: Natural sciences > Biological sciences ; Natural sciences > Computer and information sciences

Other information

Authenticus ID: P-00Q-559

DOI: 10.1074/jbc.m114.611111

Abstract (EN): Type 2 diabetes involves defective insulin secretion with islet inflammation governed in part by IL-1ß. Prolonged exposure of islets to high concentrations of IL-1ß (>24 h, 20 ng/ml) impairs beta cell function and survival. Conversely, exposure to lower concentrations of IL-1ß for >24 h improves these same parameters. The impact on insulin secretion of shorter exposure times to IL-1ßand the underlying molecular mechanisms are poorly understood and were the focus of this study. Treatment of rat primary beta cells, as well as rat or human whole islets, with 0.1 ng/ml IL-1ß for 2 h increased glucose-stimulated (but not basal) insulin secretion, whereas 20 ng/ml was without effect. Similar differential effects of IL-1ß depending on concentration were observed after 15 min of KCl stimulation but were prevented by diazoxide. Studies on sorted rat beta cells indicated that the enhancement of stimulated secretion by 0.1 ng/ml IL-1ß was mediated by the NF-ßB pathway and c-JUN/JNK pathway acting in parallel to elicit focal adhesion remodeling and the phosphorylation of paxillin independently of upstream regulation by focal adhesion kinase. Because the beneficial effect of IL-1ß was dependent in part upon transcription, gene expression was analyzed by RNAseq. There were 18 genes regulated uniquely by 0.1 but not 20 ng/ml IL-1ß, which are mostly involved in transcription and apoptosis. These results indicate that 2h of exposure of beta cells to a low but not a high concentration of IL-1ß enhances glucose-stimulated insulin secretion through focal adhesion and actin remodeling, as well as modulation of gene expression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Language: English

Type (Professor's evaluation): Scientific