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Interleukin‐6 treatment induces beta‐cell apoptosis via STAT‐3‐mediated nitric oxide production
Author(s) -
Oh Yoon Sin,
Lee YounJung,
Park Eun Young,
Jun HeeSook
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1233
Subject(s) - propidium iodide , viability assay , apoptosis , microbiology and biotechnology , interleukin , biology , endocrinology , medicine , chemistry , programmed cell death , cytokine , immunology , biochemistry
Background Type 2 diabetes is characterized by progressive beta‐cell failure and apoptosis is probably the main form of beta‐cell death in this disease. It was reported that circulating levels of interleukin‐6 are elevated in type 2 diabetic patients, but whether this is involved in the pathogenesis of type 2 diabetes is still debated. In this study, we examined whether interleukin‐6 can induce beta‐cell damage in vitro and elucidated its mechanisms. Methods To examine the effect of interleukin‐6 on beta cells, glucose‐stimulated insulin secretion (GSIS) by enzyme immunoassay (EIA) method and cell apoptosis by propidium iodide and annexin‐V staining were measured in a rat beta‐cell line (INS‐1 or INS‐832/13) after treatment with interleukin‐6. The expression of apoptosis‐related molecules was measured using western blotting and nitric oxide (NO) production was measured using Griess assay. AG490 and N ‐monomethyl‐ L ‐arginine were used to inhibit Janus kinase‐mediated signal transducers and activators of transcription signalling and NO production, respectively. Results Exposure (48 h) of INS‐1 cells to 20 ng/mL interleukin‐6 significantly decreased GSIS as well as cell viability. We found that sub‐G1/G0 population was increased as compared with untreated cells and expression of cleaved caspase‐3, cleaved poly(ADP‐ribose) polymerase, phosphorylated p38 mitogen‐activated protein kinase and phosphorylated nuclear factor‐κB was increased in interleukin‐6‐treated INS‐1 cells. Interleukin‐6 increased the amount of early apoptotic cells; this increase was blocked by AG490 or N ‐monomethyl‐ L ‐arginine treatment. Moreover, NO production, which is known to induce apoptosis, was increased by interleukin‐6 treatment but abrogated in AG490‐treated cells. Conclusion Our results show that exposure to interleukin‐6 for 48 h can induce beta‐cell death, in part via signal transducers and activators of transcription‐3‐mediated NO production. Copyright © 2011 John Wiley & Sons, Ltd.