Evaluation of the INS-1 832/13 cell line as a beta-cell based screening system to assess pollutant effects on beta-cell function
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 base...
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| creator | Hectors, Tine L M Vanparys, Caroline Pereira-Fernandes, Anna Martens, Geert A Blust, Ronny |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0060030 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0060030</identifier><identifier>PMID: 23555872</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acute effects ; Analysis ; Benzhydryl Compounds - toxicity ; Beta cells ; Biology ; Bisphenol A ; Cell culture ; Cell Line ; Chronic exposure ; Diabetes ; Diabetes mellitus ; Diazoxide - toxicity ; Ecological risk assessment ; Endocrinology ; Environmental effects ; Evaluation ; Exenatide ; Exposure ; Gene expression ; Glibenclamide ; Glucose ; Glyburide - toxicity ; Health risks ; Humans ; Hydrocarbons, Fluorinated - toxicity ; Insulin ; Insulin - metabolism ; Insulin resistance ; Insulin Secretion ; Insulin-Secreting Cells - drug effects ; Insulin-Secreting Cells - metabolism ; Medical screening ; Medicine ; Metabolic disorders ; Metabolism ; Optimization ; Pancreas ; Pancreatic beta cells ; Penicillin ; Peptides ; Peptides - toxicity ; Phenols ; Phenols - toxicity ; Phthalic Acids - toxicity ; Physiology ; Pollutants ; Pollution control ; Pollution effects ; Rankings ; Risk analysis ; Risk assessment ; Risk factors ; Rodents ; Screening ; Secretion ; Stimulators ; Sulfonamides - toxicity ; Type 2 diabetes ; Venoms - toxicity</subject><ispartof>PloS one, 2013-03, Vol.8 (3), p.e60030</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Hectors et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Hectors et al 2013 Hectors et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6d464ae3b210a5426255ef44863645ab2e20c36402e93e884747cfc9206cdf193</citedby><cites>FETCH-LOGICAL-c692t-6d464ae3b210a5426255ef44863645ab2e20c36402e93e884747cfc9206cdf193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605429/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605429/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23555872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Laudet, Vincent</contributor><creatorcontrib>Hectors, Tine L M</creatorcontrib><creatorcontrib>Vanparys, Caroline</creatorcontrib><creatorcontrib>Pereira-Fernandes, Anna</creatorcontrib><creatorcontrib>Martens, Geert A</creatorcontrib><creatorcontrib>Blust, Ronny</creatorcontrib><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</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Acute effects</subject><subject>Analysis</subject><subject>Benzhydryl Compounds - toxicity</subject><subject>Beta cells</subject><subject>Biology</subject><subject>Bisphenol A</subject><subject>Cell culture</subject><subject>Cell Line</subject><subject>Chronic exposure</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diazoxide - toxicity</subject><subject>Ecological risk assessment</subject><subject>Endocrinology</subject><subject>Environmental effects</subject><subject>Evaluation</subject><subject>Exenatide</subject><subject>Exposure</subject><subject>Gene expression</subject><subject>Glibenclamide</subject><subject>Glucose</subject><subject>Glyburide - toxicity</subject><subject>Health risks</subject><subject>Humans</subject><subject>Hydrocarbons, Fluorinated - toxicity</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin resistance</subject><subject>Insulin Secretion</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Medical screening</subject><subject>Medicine</subject><subject>Metabolic disorders</subject><subject>Metabolism</subject><subject>Optimization</subject><subject>Pancreas</subject><subject>Pancreatic beta cells</subject><subject>Penicillin</subject><subject>Peptides</subject><subject>Peptides - toxicity</subject><subject>Phenols</subject><subject>Phenols - toxicity</subject><subject>Phthalic Acids - toxicity</subject><subject>Physiology</subject><subject>Pollutants</subject><subject>Pollution control</subject><subject>Pollution effects</subject><subject>Rankings</subject><subject>Risk analysis</subject><subject>Risk assessment</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Screening</subject><subject>Secretion</subject><subject>Stimulators</subject><subject>Sulfonamides - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23555872</pmid><doi>10.1371/journal.pone.0060030</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2013-03, Vol.8 (3), p.e60030 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acute effects Analysis Benzhydryl Compounds - toxicity Beta cells Biology Bisphenol A Cell culture Cell Line Chronic exposure Diabetes Diabetes mellitus Diazoxide - toxicity Ecological risk assessment Endocrinology Environmental effects Evaluation Exenatide Exposure Gene expression Glibenclamide Glucose Glyburide - toxicity Health risks Humans Hydrocarbons, Fluorinated - toxicity Insulin Insulin - metabolism Insulin resistance Insulin Secretion Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Medical screening Medicine Metabolic disorders Metabolism Optimization Pancreas Pancreatic beta cells Penicillin Peptides Peptides - toxicity Phenols Phenols - toxicity Phthalic Acids - toxicity Physiology Pollutants Pollution control Pollution effects Rankings Risk analysis Risk assessment Risk factors Rodents Screening Secretion Stimulators Sulfonamides - toxicity Type 2 diabetes Venoms - toxicity |
| 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 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T15%3A42%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20the%20INS-1%20832/13%20cell%20line%20as%20a%20beta-cell%20based%20screening%20system%20to%20assess%20pollutant%20effects%20on%20beta-cell%20function&rft.jtitle=PloS%20one&rft.au=Hectors,%20Tine%20L%20M&rft.date=2013-03-21&rft.volume=8&rft.issue=3&rft.spage=e60030&rft.pages=e60030-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0060030&rft_dat=%3Cgale_plos_%3EA478173007%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1330891321&rft_id=info:pmid/23555872&rft_galeid=A478173007&rft_doaj_id=oai_doaj_org_article_64db1d2bbf034fa3b2ffc91312b1009d&rfr_iscdi=true |