Diaz-Ganete, AntoniaQuiroga-de-Castro, AranzazuMateos, Rosa M.Medina, FranciscoSegundo, CarmenLechuga-Sancho, Alfonso M.2022-12-142022-12-142021-03-04Diaz-Ganete A, Quiroga-de-Castro A, Mateos RM, Medina F, Segundo C, Lechuga-Sancho AM. Toxicity Induced by Cytokines, Glucose, and Lipids Increase Apoptosis and Hamper Insulin Secretion in the 1.1E7 Beta Cell-Line. Int J Mol Sci. 2021 Mar 4;22(5):25591661-6596http://hdl.handle.net/10668/4497Basic research on types 1 and 2 diabetes mellitus require early stage studies using beta cells or cell lines, ideally of human origin and with preserved insulin secretion in response to glucose. The 1.1E7 cells are a hybrid cell line resulting from the electrofusion of dispersed human islets and PANC-1 cells, capable of secreting insulin in response to glucose, but their survival and function under toxic conditions remains untested. This characterization is the purpose of the present study. We treated these cells with a cytokine mix, high glucose, palmitate, and the latter two combined. Under these conditions, we measured cell viability and apoptosis (MTT, Caspase Glo and TUNEL assays, as well as caspase-8 and -9 levels by Western blotting), endoplasmic reticulum stress markers (EIF2AK3, HSPA4, EIF2a, and HSPA5) by real-time PCR, and insulin secretion with a glucose challenge. All of these stimuli (i) induce apoptosis and ER stress markers expression, (ii) reduce mRNA amounts of 2-5 components of genes involved in the insulin secretory pathway, and (iii) abrogate the insulin release capability of 1.1E7 cells in response to glucose. The most pronounced effects were observed with cytokines and with palmitate and high glucose combined. This characterization may well serve as the starting point for those choosing this cell line for future basic research on certain aspects of diabetes.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/ApoptosisBeta cellCytokinesCytotoxicityDiabetesGlucotoxicityLipotoxicityMechanismCélulas secretoras de insulinaCitocinasCitotoxicidad inmunológicaGlucosaLípidosToxicidadMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell LineMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell SurvivalMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::CytokinesMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes MellitusMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene ExpressionMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::GlucoseMedical Subject Headings::Anatomy::Cells::Endocrine Cells::Enteroendocrine Cells::Insulin-Secreting CellsMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Palmitic Acids::PalmitatesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messengerresearch article33806355open access10.3390/ijms220525591422-0067PMC7961802