title: Low dose monoethyl phthalate (MEP) exposure triggers proliferation by activating PDX-1 at 1.1B4 human pancreatic beta cells.
abstract: Phthalate plasticizers used in a wide range of common plastic products are released into the environment and may pose a risk of increased incidence of type 2 diabetes. In this work, we studied the effects of monoethyl phthalate (MEP), the metabolite of diethyl phthalate, exposure on 1.1B4 human pancreatic beta cells at low doses (1-1000 nM). We showed that MEP treatment induced proliferation in 1.1B4 cells. Also PCNA protein expression levels were increased related to proliferation induction. It has been noted that phthalates can exert estrogen mediated response by interacting with ER. In our study 24 h MEP treatment decreased ERα protein expression level conversely it increased the same protein expression level after 72 h treatment. Also MEP treatment decreased ERβ expression after 72 h at 1.1B4 cells. Our results further show that insulin content of 1.1B4 cells were increased with low dose MEP treatment. Along with our insulin content results, PDX- 1 expression levels were also increased at 1.1B4 cells with MEP treatment. These findings suggest that MEP acts as an estrogenic compound and PPARγ agonist at lower concentrations. Also it should be noted that PDX-1 may be a critical regulator of 1.1B4 cells treated with MEP.
authors.affiliation: Department of Biophysic, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey.
authors.forename: Celal
authors.initials: C
authors.lastname: Güven
authors.affiliation: Department of Biophysic, Faculty of Medicine, Haliç University, Istanbul, Turkey; Department of Biophysic, Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Fulya
authors.initials: F
authors.lastname: Dal
authors.affiliation: Department of Biology, Faculty of Science, University of Hacettepe, Ankara, Turkey. Electronic address: mufideaydogan@gmail.com.
authors.forename: Müfide
authors.initials: M
authors.lastname: Aydoğan Ahbab
authors.affiliation: Department of Physiotherapy and Rehabilitation, School of Health Sciences, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Eylem
authors.initials: E
authors.lastname: Taskin
authors.affiliation: Internal Medicine Clinic, Haseki Training and Research Hospital, Istanbul, Turkey.
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ahbab
authors.affiliation: Department of Immunology, Institute of Experimental Medicine Research, Istanbul University, Istanbul, Turkey.
authors.forename: Suzan
authors.initials: S
authors.lastname: Adin Çinar
authors.affiliation: Department of Genetics, Institute of Experimental Medicine Research, Istanbul University, Istanbul, Turkey.
authors.forename: Sema
authors.initials: S
authors.lastname: Sırma Ekmekçi
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Çağrı
authors.initials: Ç
authors.lastname: Güleç
authors.affiliation: Department of Genetics, Institute of Experimental Medicine Research, Istanbul University, Istanbul, Turkey.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Abacı
authors.affiliation: Department of Biophysic, Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Handan
authors.initials: H
authors.lastname: Akçakaya
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010795:Phthalic Acids / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D010795:Phthalic Acids; D015534:Trans-Activators; C581825:monoethyl phthalate; C084010:pancreatic and duodenal homeobox 1 protein
keywords: 1.1B4 cells; Diabetes; Mechanisms; Monoethyl phthalate; PDX-1; Toxicity