Toxicity Induced by Cytokines, Glucose, and Lipids Increase Apoptosis and Hamper Insulin Secretion in the 1.1E7 Beta Cell-Line
| Autor: | Aranzazu Quiroga-de-Castro, Alfonso M. Lechuga-Sancho, Antonia Diaz-Ganete, Carmen Segundo, Rosa M. Mateos, Francisco Medina |
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| Přispěvatelé: | Biomedicina, Biotecnología y Salud Pública, Materno-Infantil y Radiología, [Diaz-Ganete,A, Mateos,RM, Medina,F, Segundo,C, Lechuga-Sancho,AM] Inflammation, Nutrition, Metabolism and Oxidative Stress Study Group (INMOX), Biomedical Research and Innovation Institute of Cádiz (INiBICA), Research Unit, Puerta del Mar University Hospital, Cádiz, Spain. [Quiroga-de-Castro,A, Lechuga-Sancho,AM] Area of Pediatrics, Department of Child and Mother Health and Radiology, Medical School, University of Cádiz, Cádiz, Spain. [Mateos,RM] Area of Biochemistry and Molecular Biology, Department of Biomedicine, Biotechnology and Public Health, University of Cádiz, Cádiz, Spain. [Medina,F, Segundo,C] Salus Infirmorum Faculty of Nursing, Cadiz University, Cadiz, Spain. [Lechuga-Sancho,AM] Pediatric Endocrinology, Department of Pediatrics, Puerta del Mar University Hospital, Cádiz, Spain., This research was funded by grants by the Andalusian Department of Health (PI 0765-2011 and PI-0269-2014) to A.M.L.-S. A.D.-G. was funded by an intramural grant from the Foundation for Biomedical Research in Cadiz. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Citotoxicidad inmunológica medicine.medical_treatment Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose [Medical Subject Headings] Palmitates Gene Expression Apoptosis Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings] lcsh:Chemistry 0302 clinical medicine Anatomy::Cells::Cells Cultured::Cell Line [Medical Subject Headings] Insulin-Secreting Cells Insulin Secretion lcsh:QH301-705.5 Endoplasmic Reticulum Chaperone BiP Spectroscopy Chemicals and Drugs::Lipids::Fatty Acids::Palmitic Acids::Palmitates [Medical Subject Headings] diabetes Chemistry apoptosis Citocinas General Medicine lipotoxicity Endoplasmic Reticulum Stress Computer Science Applications Cytokine Lipotoxicity Lípidos Cytokines cytotoxicity Beta cell medicine.medical_specialty Cell Survival mechanism 030209 endocrinology & metabolism Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus [Medical Subject Headings] Catalysis Article Cell Line Inorganic Chemistry 03 medical and health sciences glucotoxicity Células secretoras de insulina Internal medicine Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Survival [Medical Subject Headings] medicine Diabetes Mellitus Humans Viability assay RNA Messenger Physical and Theoretical Chemistry Molecular Biology Secretory pathway Chemicals and Drugs::Amino Acids Peptides and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines [Medical Subject Headings] Anatomy::Cells::Endocrine Cells::Enteroendocrine Cells::Insulin-Secreting Cells [Medical Subject Headings] Insulin Organic Chemistry Toxicidad Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Nucleic Acids::RNA::RNA Messenger [Medical Subject Headings] beta cell cytokines Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings] 030104 developmental biology Endocrinology Glucose lcsh:Biology (General) lcsh:QD1-999 Glucosa Unfolded protein response |
| Zdroj: | Int. J. Mol. Sci. 2021, 22(5), 2559 International Journal of Molecular Sciences RODIN. Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz instname International Journal of Molecular Sciences, Vol 22, Iss 2559, p 2559 (2021) RODIN: Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz Universidad de Cádiz Volume 22 Issue 5 |
| ISSN: | 0765-2011 |
| Popis: | Basic 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. This research was funded by grants by the Andalusian Department of Health (PI 0765-2011 and PI-0269-2014) to A.M.L.-S. A.D.-G. was funded by an intramural grant from the Foundation for Biomedical Research in Cadiz. No external funding for APC was available. |
| Databáze: | OpenAIRE |
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