| L-arginine is essential for pancreatic beta-cell functional integrity, metabolism and defence from inflammatory challenge. | |
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MedLine Citation:
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PMID: 21784771 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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+GSSG) anti-oxidant responses, stimulus-secretion coupling, and functional integrity. Clonal BRIN-BD11 β cells and mouse islets were cultured for 24h at various L-arginine concentrations (0 to 1.15mmol L-1) in the absence or presence of a pro-inflammatory cytokine cocktail (IL-1β, TNFα, IFNγ). Cells were assessed for viability, insulin secretion, GSH, GSSG, glutamate, NO, superoxide, urea, lactate, and for the consumption of glucose and glutamine. Protein levels of NO synthase (NOS-2), AMPK and the HSP72 were also evaluated. We found that L arginine at 1.15 mmol L-1 attenuated the loss of β-cell viability observed in the presence of pro-inflammatory cytokines. L arginine increased total cellular glutathione 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. Pro-inflammatory cytokines reduced, by at least 50%, chronic (24h) insulin secretion, an effect partially attenuated by 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, anti-oxidant and protective responses, enabling increased functional integrity of β cells and islets in the presence of pro-inflammatory cytokines. Glucose consumption and intermediary metabolism were increased by L-arginine. These results highlight the importance of L-arginine availability for beta-cells during inflammatory challenge. |
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Authors:
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Mauricio Krause; Nh McClenaghan; Peter R Flatt; Paulo Ivo Homem de Bittencourt; Colin Murphy; Philip Newsholme |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-22 |
Journal Detail:
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Title: The Journal of endocrinology Volume: - ISSN: 1479-6805 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375363 Medline TA: J Endocrinol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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M Krause, Science, Institute of Technology Tallaght, Dublin, Dublin 24, Ireland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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