title: Evaluation of the INS-1 832/13 cell line as a beta-cell based screening system to assess pollutant effects on beta-cell function.
abstract: Environmental pollutants have recently emerged as potential risk factors for metabolic diseases, urging systematic investigation of pollutant effects on metabolic disease processes. To enable risk assessment of these so-called metabolic disruptors the use of stable, robust and well-defined cell based screening systems has recently been encouraged. Since beta-cell (dys)functionality is central in diabetes pathophysiology, the need to develop beta-cell based pollutant screening systems is evident. In this context, the present research evaluated the strengths and weaknesses of the INS-1 832/13 pancreatic beta-cell line as diabetogenic pollutant screening system with a focus on beta-cell function. After optimization of exposure conditions, positive (exendin-4, glibenclamide) and negative (diazoxide) control compounds for acute insulin secretion responses were tested and those with the most profound effects were selected to allow potency estimations and ranking of pollutants. This was followed by a first explorative screening of acute bisphenol A and bis(2-ethylhexyl)phthalate effects. The same approach was applied for chronic exposures, focusing primarily on evaluation of acknowledged chronic stimulators (diazoxide, T0901317, exendin-4) or inhibitors (glibenclamide) of insulin secretion responses to select the most responsive ones for use as control compounds in a chronic pollutant testing framework. Our results showed that INS-1 832/13 cells responded conform previous observations regarding acute effects of control compounds on insulin secretion, while bisphenol A and bis(2-ethylhexyl)phthalate had limited acute effects. Furthermore, chronic exposure to known beta-cell reactive compounds resulted in deviating insulin secretion and insulin content profiles compared to previous reports. In conclusion, this INS-1 subclone appears to lack certain characteristics needed to respond appropriately to acute pollutant exposure or long term exposure to known beta-cell reactive compounds and thus seems to be, in our setting, inadequate as a diabetogenic pollutant screening system.
authors.affiliation: Systemic Physiological and Ecotoxicological Research, Department of Biology, University of Antwerp, Antwerp, Belgium. tine.hectors@ua.ac.be
authors.forename: Tine L M
authors.initials: TL
authors.lastname: Hectors
authors.forename: Caroline
authors.initials: C
authors.lastname: Vanparys
authors.forename: Anna
authors.initials: A
authors.lastname: Pereira-Fernandes
authors.forename: Geert A
authors.initials: GA
authors.lastname: Martens
authors.forename: Ronny
authors.initials: R
authors.lastname: Blust
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity; D002460:Cell Line; D003981:Diazoxide / Q000633:toxicity; D000077270:Exenatide; D005905:Glyburide / Q000633:toxicity; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000633:toxicity; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D010455:Peptides / Q000633:toxicity; D010636:Phenols / Q000633:toxicity; D010795:Phthalic Acids / Q000633:toxicity; D013449:Sulfonamides / Q000633:toxicity; D014688:Venoms / Q000633:toxicity; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003981:Diazoxide; D000077270:Exenatide; D005905:Glyburide; D006845:Hydrocarbons, Fluorinated; D007328:Insulin; D010455:Peptides; D010636:Phenols; D010795:Phthalic Acids; D013449:Sulfonamides; D014688:Venoms; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C570653:bis(2-ethyltridecyl)phthalate; C006780:bisphenol A; D000098826:Bisphenol A Compounds
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