RT Journal Article T1 Toxicity Induced by Cytokines, Glucose, and Lipids Increase Apoptosis and Hamper Insulin Secretion in the 1.1E7 Beta Cell-Line A1 Diaz-Ganete, Antonia A1 Quiroga-de-Castro, Aranzazu A1 Mateos, Rosa M. A1 Medina, Francisco A1 Segundo, Carmen A1 Lechuga-Sancho, Alfonso M. K1 Apoptosis K1 Beta cell K1 Cytokines K1 Cytotoxicity K1 Diabetes K1 Glucotoxicity K1 Lipotoxicity K1 Mechanism K1 Células secretoras de insulina K1 Citocinas K1 Citotoxicidad inmunológica K1 Glucosa K1 Lípidos K1 Toxicidad AB 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. PB MDPI SN 1661-6596 YR 2021 FD 2021-03-04 LK http://hdl.handle.net/10668/4497 UL http://hdl.handle.net/10668/4497 LA en NO Diaz-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):2559 DS RISalud RD Apr 14, 2025