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    Physiological concentrations of interleukin-6 directly promote insulin secretion, signal transduction, nitric oxide release, and redox status in a clonal pancreatic ß-cell line and mouse islets

    Access Status
    Open access via publisher
    Authors
    Da Silva Krause, M.
    Bittencourt, A.
    de Bittencourt, P.
    McClenaghan, N.
    Flatt, P.
    Murphy, C.
    Newsholme, Philip
    Date
    2012
    Type
    Journal Article
    
    Metadata
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    Citation
    Da Silva Krause, Mauricio and Bittencourt, Aline and de Bittencourt, Paulo Ivo Homem and McClenaghan, Neville H. and Flatt, Peter R. and Murphy, Colin and Newsholme, Philip. 2012. Physiological concentrations of interleukin-6 directly promote insulin secretion, signal transduction, nitric oxide release, and redox status in a clonal pancreatic ß-cell line and mouse islets. Journal of Endocrinology. 214: pp. 301-311.
    Source Title
    Journal of Endocrinology
    DOI
    10.1530/JOE-12-0223
    ISSN
    0022-0795
    URI
    http://hdl.handle.net/20.500.11937/19062
    Collection
    • Curtin Research Publications
    Abstract

    Interleukin-6 (IL6) has recently been reported to promote insulin secretion in a glucagon-like peptide-1-dependent manner. Herein, the direct effects of IL6 (at various concentrations from 0 to 1000 pg/ml) on pancreatic β-cell metabolism, AMP-activated protein kinase (AMPK) signaling, insulin secretion, nitrite release, and redox status in a rat clonal β-cell line and mouse islets are reported. Chronic insulin secretion (in μg/mg protein per 24 h) was increased from 128.7±7.3 (no IL6) to 178.4±7.7 (at 100 pg/ml IL6) in clonal β-cells and increased significantly in islets incubated in the presence of 5.5 mM glucose for 2 h, from 0.148 to 0.167±0.003 ng/islet. Pretreatment with IL6 also induced a twofold increase in basal and nutrient-stimulated insulin secretion in subsequent 20 min static incubations. IL6 enhanced both glutathione (GSH) and glutathione disulphide (GSSG) by nearly 20% without changing intracellular redox status (GSSG/GSH). IL6 dramatically increased iNOS expression (by ca. 100-fold) with an accompanying tenfold rise in nitrite release in clonal β-cells. Phosphorylated AMPK levels were elevated approximately twofold in clonal β-cells and mouse islet cells. Calmodulin-dependent protein kinase kinase levels (CaMKK), an upstream kinase activator of AMPK, were also increased by 50% after IL6 exposure (in β-cells and islets). Our data have demonstrated that IL6 can stimulate β-cell-dependent insulin secretion via direct cell-based mechanisms. AMPK, CaMKK (an upstream kinase activator of AMPK), and the synthesis of nitric oxide appear to alter cell metabolism to benefit insulin secretion. In summary, IL6 exerts positive effects on β-cell signaling, metabolism, antioxidant status, and insulin secretion.

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