Effects of the microbial secondary metabolites pyrrolnitrin, phenazine and patulin on INS-1 rat pancreatic β-cells

Raid B. Nisr (Lead / Corresponding author), Mark A. Russell, Abdesslam Chrachri, A. John Moody, Martyn L. Gilpin

    Research output: Contribution to journalArticlepeer-review

    9 Citations (Scopus)

    Abstract

    The effects on pancreatic β-cell viability and function of three microbial secondary metabolites pyrrolnitrin, phenazine and patulin were investigated, using the rat clonal pancreatic β-cell line, INS-1. Cells were exposed to 10-fold serial dilutions (range 0-10 μg mL-1) of the purified compounds for 2, 24 and 72 h. After 2 h exposure, only patulin (10 μg mL-1) was cytotoxic. All compounds showed significant cytotoxicity after 24 h. None of the compounds altered insulin secretion with 2 and 20 mM glucose after 2 h. However, after 24 h treatment, phenazine and pyrrolnitrin (10 and 100 ng mL-1) potentiated insulin production and glucose-stimulated insulin secretion, whereas patulin had no effect. Exposure (24 h) to either phenazine (100 ng mL-1) or pyrrolnitrin (10 ng mL-1) caused similar increases in the Ca2+ content of INS-1 cells. The outward membrane current was inhibited after 24 h exposure to either phenazine (100 ng mL-1) or pyrrolnitrin (10 or 100 ng mL-1). This study presents novel data suggesting that high concentrations of pyrrolnitrin and phenazine are cytotoxic to pancreatic β-cells and thus possibly diabetogenic, whereas at lower concentrations these agents are nontoxic and may be insulinotropic. The possible role of such agents in the development of cystic fibrosis-related diabetes is discussed.

    Original languageEnglish
    Pages (from-to)217-227
    Number of pages11
    JournalFEMS Immunology and Medical Microbiology
    Volume63
    Issue number2
    DOIs
    Publication statusPublished - 1 Nov 2011

    Keywords

    • Burkholderia
    • Diabetes
    • Infection
    • INS-1 cells
    • Insulin synthesis
    • Patch clamp

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Microbiology
    • Immunology
    • Microbiology (medical)
    • Infectious Diseases

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