title: Effects of the microbial secondary metabolites pyrrolnitrin, phenazine and patulin on INS-1 rat pancreatic β-cells.
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 Ca(2+) 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.
authors.affiliation: Centre for Research in Translational Biomedicine, School of Biomedical and Biological Sciences, University of Plymouth, Plymouth, UK. raid.nisr@plymouth.ac.uk
authors.forename: Raid B
authors.initials: RB
authors.lastname: Nisr
authors.forename: Mark A
authors.initials: MA
authors.lastname: Russell
authors.forename: Abdesslam
authors.initials: A
authors.lastname: Chrachri
authors.forename: A John
authors.initials: AJ
authors.lastname: Moody
authors.forename: Martyn L
authors.initials: ML
authors.lastname: Gilpin
mesh_terms: D000818:Animals; D001419:Bacteria / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D010365:Patulin / Q000378:metabolism / Q000633:toxicity*; D010619:Phenazines / Q000378:metabolism / Q000633:toxicity*; D011764:Pyrrolnitrin / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
chemical_list: D007328:Insulin; D010619:Phenazines; D010365:Patulin; D011764:Pyrrolnitrin; D002118:Calcium