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

• Published in: FEMS immunology and medical microbiology Vol. 63; no. 2; pp. 217 - 227
• Main Authors: Nisr, Raid B., Russell, Mark A., Chrachri, Abdesslam, Moody, A. John, Gilpin, Martyn L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2011; Blackwell; Oxford University Press
• Subjects: Animals; Bacteria - chemistry; Bacteria - metabolism; Bacteriology; Beta cells; Biological and medical sciences; Burkholderia; Calcium; Calcium - analysis; Calcium ions; Cell Line; Cell Survival - drug effects; Cell viability; Cystic fibrosis; Cytotoxicity; diabetes; Diabetes mellitus; Exposure; Fundamental and applied biological sciences. Psychology; Glucose; infection; Insulin; Insulin - metabolism; Insulin Secretion; insulin synthesis; Insulin-Secreting Cells - chemistry; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; INS‐1 cells; Membrane Potentials - drug effects; Metabolites; Microbiology; Microorganisms; Miscellaneous; Pancreas; patch clamp; Patulin; Patulin - metabolism; Patulin - toxicity; Phenazine; Phenazines - metabolism; Phenazines - toxicity; Pyrrolnitrin - metabolism; Pyrrolnitrin - toxicity; Rats; Secondary metabolites; Secretion; Time Factors; Toxicity; INS-1 cells; infection; patch clamp; insulin synthesis; diabetes; Endocrinopathy; Pancreatic hormone; Pyrrolnitrin; Rat; Metabolite; Diabetes mellitus; Mycotoxin; Rodentia; Insulin; Patulin; Toxin; Vertebrata; Antifungal agent; Mammalia; Immunology; Bacteria; Burkholderia
• ISSN: 0928-8244; 1574-695X; 2049-632X
• DOI: 10.1111/j.1574-695X.2011.00844.x

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.