Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    L-Arginine is essential for pancreatic β-cell functional integrity, metabolism and defense from inflammatory challenge

    Access Status
    Open access via publisher
    Authors
    Krause, M.
    McClenaghan, N.
    Flatt, P.
    Hamem de Bittencourt, P.
    Murphy, C.
    Newsholme, Philip
    Date
    2011
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Krause, Mauricio S. and McClenaghan, Neville H. and Flatt, Peter R. and Hamem de Bittencourt, Paulo and Murphy, Colin and Newsholme, Philip. 2011. L-Arginine is essential for pancreatic β-cell functional integrity, metabolism and defense from inflammatory challenge. Journal of Endocrinology. 211: pp. 87-97.
    Source Title
    Journal of Endocrinology
    DOI
    10.1530/JOE-11-0236
    ISSN
    0022-0795
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/42587
    Collection
    • Curtin Research Publications
    Abstract

    In this work, our aim was to determine whether L-arginine (a known insulinotropic amino acid) can promote a shift of β-cell intermediary metabolism favoring glutathione (GSH) and glutathione disulfide (GSSG) antioxidant responses, stimulus–secretion coupling and functional integrity. Clonal BRIN-BD11 β-cells and mouse islets were cultured for 24 h at various L-arginine concentrations (0–1.15 mmol/l) in the absence or presence of a proinflammatory cytokine cocktail (interleukin 1β, tumour necrosis factor α and interferon γ). Cells were assessed for viability, insulin secretion, GSH, GSSG, glutamate, nitric oxide (NO), superoxide, urea, lactate and for the consumption of glucose and glutamine. Protein levels of NO synthase-2, AMP-activated protein kinase (AMPK) and the heat shock protein 72 (HSP72) were also evaluated. We found that L-arginine at 1.15 mmol/l attenuated the loss of β-cell viability observed in the presence of proinflammatory cytokines. L-Arginine increased total cellular GSH and glutamate levels but reduced the GSSG/GSH ratio and glutamate release. The amino acid stimulated glucose consumption in the presence of cytokines while also stimulating AMPK phosphorylation and HSP72 expression. Proinflammatory cytokines reduced, by at least 50%, chronic (24 h) insulin secretion, an effect partially attenuated b y L-arginine. Acute insulin secretion was robustly stimulated by L-arginine but this effect was abolished in the presence of cytokines. We conclude that L-arginine can stimulate β-cell insulin secretion, antioxidant and protective responses, enabling increased functional integrity of β-cells and islets in the presence of proinflammatory cytokines. Glucose consumption and intermediary metabolism were increased by L-arginine. These results highlight the importance of L-arginine availability for β-cells during inflammatory challenge.

    Related items

    Showing items related by title, author, creator and subject.

    • Alanyl-glutamine improves pancreatic ß-cell function following ex vivo inflammatory challenge
      Cruzat, Vinicius; Keane, Kevin; Scheinpflug, A.; Cordeiro, R.; Soares, M.; Newsholme, Philip (2015)
      Obesity-associated diabetes and concomitant inflammation may compromise pancreatic β-cell integrity and function. l-glutamine and l-alanine are potent insulin secretagogues, with antioxidant and cytoprotective properties. ...
    • 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
      Da Silva Krause, M.; Bittencourt, A.; de Bittencourt, P.; McClenaghan, N.; Flatt, P.; Murphy, C.; Newsholme, Philip (2012)
      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 ...
    • Elevated levels of branched-chain amino acids have little effect on pancreatic islet cells, but L-arginine impairs function through activation of the endoplasmic reticulum stress response
      Mullooly, N.; Vernon, W.; Smith, D.; Newsholme, Philip (2014)
      New Findings - What is the central question of this study?: Recent studies have demonstrated strong correlations between circulating branched-chain amino acid (AA) levels and insulin resistance, a predictor of susceptibility ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.