Short-term exposure of beta cells to low concentrations of Interleukin-1beta improves insulin secretion through focal adhesion and actin remodeling, and regulation of gene expression [Cell Biology]

January 13th, 2015 by Arous, C., Ferreira, P. G., Dermitzakis, E. T., Halban, P. A.

Type 2 diabetes involves defective insulin secretion with islet inflammation governed in part by IL-1beta. Prolonged exposure of islets to high concentrations of IL-1beta (>24 h, 20 ng/ml) impairs beta cell function and survival. Conversely, exposure to lower concentrations of IL-1beta for >24 h improves these same parameters. The impact on insulin secretion of shorter exposure times to IL-1beta and 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-1beta for 2 h increased glucose-stimulated (but not basal) insulin secretion whereas 20 ng/ml was without effect. Similar differential effects of IL-1beta depending on concentration were observed after 15 min KCl stimulation but prevented by diazoxide. Studies on sorted rat beta cells indicated that the enhancement of stimulated secretion by 0.1 ng/ml IL-1beta was mediated by the NF-кB 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. Since the beneficial effect of IL-1beta 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-1beta, which are mostly involved in transcription and apoptosis. These results indicate that 2 h exposure of beta cells to a low but not a high concentration of IL-1beta enhances glucose-stimulated insulin secretion through focal adhesion and actin remodeling as well as modulation of gene expression.
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