English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The proinflammatory cytokines interleukin-1β (IL-1β), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) are toxic to pancreatic β-cells and are implicated in the pathogenesis of type 1 diabetes. We have previously found that GH and prolactin (PRL) stimulate both proliferation and insulin production in pancreatic β-cells and rat insulin-producing INS-1 cells. Here we report that human (h) GH can prevent the apoptotic effects of IL-1β, IFN-γ and TNF-α in INS-1 and INS-1E cells. Using adenovirus-mediated gene transfer, we found that the anti-apoptotic effect of hGH is abrogated by expression of a dominant negative signal transducer and activator of transcription (STAT5) mutant in INS-1E cells. hGH and the cytotoxic cytokines was found to additively increase suppressor of cytokine signalling-3 mRNA expression after 4 h of exposure. In order to identify possible targets for the STAT5-mediated protection of INS-1E cells, we studied the effect of hGH on activation of the transcription factors STAT1 and nuclear factor-κB (NF-κB) by IFN-γ and IL-1β+TNF-α respectively. Gel retardation experiments showed that hGH affects neither IFN-γ+ TNF-α-induced STAT1 DNA binding nor IL-1β and IFN-γ+TNF-α-induced NFκB DNA binding. The lack of influence of hGH on cytokine-mediated activation of STAT1 and NFκB is in accordance with the finding that hGH had only a minor effect on cytokine-induced inducible nitric oxide synthase (iNOS) gene expression and in fact augmented the IL-1β-stimulated nitric oxide production. As the anti-apoptotic Bcl-x L  gene has been shown to harbour a STAT5-binding element we measured the expression of Bcl-x L  as well as the pro-apoptotic Bax. We found that hGH increased the Bcl-x L /Bax ratio both in the absence and in the presence of cytotoxic cytokines. In conclusion, these results suggested that GH and PRL protect β-cells against cytotoxic cytokines via STAT5-dependent mechanisms distal to iNOS activation possibly at the level of Bcl-x L .

journal of endocrinology/journal of endocrinology

STAT5 activation by human GH protects insulin-producing cells against interleukin-1β, interferon-γ and tumour necrosis factor-α-induced apoptosis independent of nitric oxide production