The DOI matches its Crossref record; 41 of the 45 references it cites were found in a registry or an index.
Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone
Abstract
IL-6 has emerged as an important cytokine upregulated in states of insulin resistance such as type 2 diabetes. We evaluated the chronic effect of IL-6 on insulin signaling in 3T3-F442A and 3T3-L1 adipocytes. First, cells responded to a chronic treatment with IL-6 by initiating an autoactivation process that increased IL-6 secretion. Second, IL-6-treated adipocytes showed a decreased protein expression of IR-beta subunit and IRS-1 but also an inhibition of the insulin-induced activation of IR-beta, Akt/PKB, and ERK1/2. Moreover, IL-6 suppressed the insulin-induced lipogenesis and glucose transport consistent with a diminished expression of GLUT4. IL-6-treated adipocytes failed to maintain their adipocyte phenotype as shown by the downregulation of the adipogenic markers FAS, GAPDH, aP2, PPAR-gamma, and C/EBP-alpha. IL-6 also induced the expression of SOCS-3, a potential inhibitor of insulin signaling. Finally, the effects of IL-6 could be prevented by rosiglitazone, an insulin-sensitizing agent. Thus, IL-6 may play an important role in the set-up of insulin resistance in adipose cell.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Gene expression studies with human adipose tissue have demonstrated that the levels of expression of MCP-1, colony-stimulating factor-3 and the urokinase plasminogen activator CD87 increase significantly in the adipose tissue of subjects with morbid obesity (31) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
In the citing paper
“In obese subjects, these macrophages typically aggregate in crowns around apoptotic adipocytes (31) (Figs. 1 and 2).”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
In the citing paper
“Hypoxia-inducible factor-1a, a transcription factor normally induced by hypoxia, is overexpressed in the subcutaneous adipose tissue of obese subjects and its expression is decreased during weight reduction (31) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
In the citing paper
“In this study, the protein expression of IL-10 increased, suggesting a possible M1 to M2 (pro-inflammatory to anti-inflammatory) switch of macrophage phenotypes (31) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
In the citing paper
“On the other hand, it seems likely that reduced secretion of pro-inflammatory mediators from adipocytes or activated macrophages of adipose tissue contributes to the effect of weight loss (31,36,65,67,142) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
In the citing paper
“The parallelism between the down-regulation of these genes and the reduction in adiposity and adipocyte diameter by n-3 PUFA treatment suggests a positive relationship between adipose cell size and adipose tissue inflammation, agreeing with other observations (31,66) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
Citations
Cites
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L., & Spiegelman, B. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117936 · Cited by 3,543
Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.271.5249.665 · Cited by 2,630
A family of cytokine-inducible inhibitors of signalling
Starr, R., Willson, T. A., Viney, E. M., Murray, L. J. L., Rayner, J. R., Jenkins, B. J., Gonda, T. J., Alexander, W. S., Metcalf, D., Nicola, N. A., et al. (1997) · Nature · doi:10.1038/43206 · Cited by 2,066
Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-α,in Vivo1
Mohamed‐Ali, V., Goodrick, S., Rawesh, A., Katz, D. R., Miles, J. M., Yudkin, J. S., Klein, S., & Coppack, S. W. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4450 · Cited by 2,032
Kern, P. A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.5.e745 · Cited by 1,883
Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?
Yudkin, J. S., Kumari, M., Humphries, S. E., & Mohamed-Ali, V. (2000) · Atherosclerosis · doi:10.1016/s0021-9150(99)00463-3 · Cited by 1,775
Fried, S. K., Bunkin, D. A., & Greenberg, A. S. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.3.4660 · Cited by 1,756
PPAR-gamma: adipogenic regulator and thiazolidinedione receptor.
Spiegelman, B. M. (1998) · Diabetes · doi:10.2337/diabetes.47.4.507 · Cited by 1,730
Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130
Taga, T., Hibi, M., Hirata, Y., Yamasaki, K., Yasukawa, K., Matsuda, T., Hirano, T., & Kishimoto, T. (1989) · Cell · doi:10.1016/0092-8674(89)90438-8 · Cited by 1,396
Bastard, J., Jardel, C., Bruckert, É., Blondy, P., Capeau, J., Laville, M., Vidal, H., & Hainque, B. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.9.6839 · Cited by 1,124
Self-citationWu, Z., Rosen, E. D., Brun, R. P., Hauser, S., Adelmant, G., Troy, A. E., McKeon, C., Darlington, G., & Spiegelman, B. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80306-8 · Cited by 1,015
Interleukin-6 induces cellular insulin resistance in hepatocytes.
Senn, J. J., Klover, P. J., Nowak, I. A., & Mooney, R. A. (2002) · Diabetes · doi:10.2337/diabetes.51.12.3391 · Cited by 883
Circulating Interleukin‐6 in Relation to Adiposity, Insulin Action, and Insulin Secretion
Vozarova, B., Weyer, C., Hanson, K. A., Tataranni, P. A., Bogardus, C., & Pratley, R. E. (2001) · Obesity Research · doi:10.1038/oby.2001.54 · Cited by 637
Bastard, J., Maachi, M., Nhieu, J. T. V., Jardel, C., Bruckert, É., Grimaldi, A., Robert, J., Capeau, J., & Hainque, B. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.5.8450 · Cited by 636
Self-citationSenn, J. J., Klover, P. J., Nowak, I. A., Zimmers, T. A., Koniaris, L. G., Furlanetto, R. W., & Mooney, R. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210689200 · Cited by 620
Fernandez-Real, J.-M., Vayreda, M., Richart, C., Gutierrez, C., Broch, M., Vendrell, J., & Ricart, W. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.3.7305 · Cited by 567
Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes
Faßhauer, M., Kralisch, S., Klier, M., Lössner, U., Blüher, M., Klein, J. C., & Paschke, R. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00090-1 · Cited by 538
SOCS-3 Is an Insulin-induced Negative Regulator of Insulin Signaling
Emanuelli, B., Peraldi, P., Filloux, C., Sawka‐Verhelle, D., Hilton, D. J., & OBBERGHEN, E. V. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.21.15985 · Cited by 468
Emanuelli, B., Peraldi, P., Filloux, C., Carine Chavey, A., Freidinger, K., Hilton, D. J., Hotamışlıgil, G. S., & OBBERGHEN, E. V. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104602200 · Cited by 449
The role of TNFα in adipocyte metabolism
Sethi, J. K., & Hotamışlıgil, G. S. (1999) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.1998.0273 · Cited by 433
The mode of action of thiazolidinediones
Hauner, H. (2002) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.249 · Cited by 412
Distinct Transcriptional Profiles of Adipogenesisin Vivo and in Vitro
Soukas, A. A., Socci, N. D., Saatkamp, B. D., Novelli, S. E., & Friedman, J. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104421200 · Cited by 368
Müller, S., Martin, S., Koenig, W., Hanifi-Moghaddam, P., Rathmann, W., Haastert, B., Giani, G., Illig, T., Thorand, B., & Kolb, H. (2002) · Diabetologia · doi:10.1007/s00125-002-0829-2 · Cited by 311
Caron, M., Auclair, M., Vigouroux, C., Glorian, M., Forest, C. D., & Capeau, J. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1378 · Cited by 308
Self-citationGreenberg, A. S., Nordan, R. P., McIntosh, J. K., Calvo, J. C., Scow, R. O., & Jablons, D. M. (1992) · PubMed · Cited by 277
Molecular regulation of adipocyte differentiation
Cowherd, R. M., Lyle, R. E., & McGehee, R. E. (1999) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.1998.0276 · Cited by 270
Kaestner, K. H., Christy, R. J., & Lane, M. D. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.1.251 · Cited by 268
Regulation of adipose cell differentiation. I. Fatty acids are inducers of the aP2 gene expression.
Amri, E., Bertrand, B., Ailhaud, G. P., & Grimaldi, P. A. (1991) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41912-1 · Cited by 243
The metabolic effects of tumor necrosis factor and other cytokines
Grünfeld, C., & Feingold, K. R. (1991) · Biotherapy · doi:10.1007/bf02172087 · Cited by 194
Klouche, M., Bhakdi, S., Hemmes, M., & Rose‐John, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.8.4583 · Cited by 178
Mediators of inflammation and acute phase response in the liver.
Streetz, K. L., Wüstefeld, T., Klein, C., Manns, M. P., & Trautwein, C. (2001) · PubMed · Cited by 175
Lay, S. L., Lefrère, I., Trautwein, C., Dugail, I., & Krief, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203913200 · Cited by 172
Päth, G., Bornstein, S. R., Gurniak, M., Chrousos, G. P., Scherbaum, W. A., & Hauner, H. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.5.7494 · Cited by 150
Insulin and Rosiglitazone Regulation of Lipolysis and Lipogenesis in Human Adipose Tissue In Vitro
McTernan, P. G., Harte, A. L., Anderson, L. A., Green, A., Smith, S. A., Holder, J. C., Barnett, A. H., Eggo, M. C., & Kumar, S. (2002) · Diabetes · doi:10.2337/diabetes.51.5.1493 · Cited by 128
Tanaka, T., Itoh, H., Doi, K., Fukunaga, Y., Hosoda, K., Shintani, M., Yamashita, J. K., Chun, T., Inoue, M., Masatsugu, K., et al. (1999) · Diabetologia · doi:10.1007/s001250051218 · Cited by 124
Gustafson, B., Jack, M. M., Cushman, S. W., & Smith, U. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01518-3 · Cited by 117
Stimulation of interleukin-6 release by interleukin-1β from isolated human adipocytes
Flower, L., Gray, R. P., Pinkney, J. H., & Mohamed‐Ali, V. (2003) · Cytokine · doi:10.1016/s1043-4666(02)00495-7 · Cited by 74
Alvarez, B., Quinn, L. S., Busquets, S., Quiles, M., López-Soriano, F. J., & Argilés, J. M. A. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(01)00167-7 · Cited by 66
Peraldi, P., Filloux, C., Emanuelli, B., Hilton, D. J., & OBBERGHEN, E. V. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102209200 · Cited by 61
Metabolic and Endocrine Actions of Interleukin‐1.
Besedovsky, H. O., & del Rey, A. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb40481.x · Cited by 19
Cited by
Sorted by citations
Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388
Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
Cai, D., Yuan, M., Frantz, D. F., Melendez, P. A., Hansen, L., Lee, J., & Shoelson, S. E. (2005) · Nature Medicine · doi:10.1038/nm1166 · Cited by 2,245
Recent advances in the relationship between obesity, inflammation, and insulin resistance.
Bastard, J., Maachi, M., Lagathu, C., Kim, M. J., Caron, M., Vidal, H., Capeau, J., & Fève, B. (2006) · PubMed · Cited by 2,090
Self-citationInflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes
Zatterale, F., Longo, M., Naderi, J., Raciti, G. A., Desiderio, A., Miele, C., & Beguinot, F. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2019.01607 · Cited by 1,180
Metadata
- Authors
- Lagathu, C., Bastard, J.-P., Auclair, M., Maachi, M., Capeau, J., & Caron, M.
- Affiliations
- Inserm (FR)
- Corresponding author
- Caron, Martine
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 311
- Issue
- 2
- Pages
- 372-379
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2061613314
- Cited by
- 385
- References
- 45
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 15 · 2023: 11 · 2022: 15 · 2021: 9 · 2020: 12 · 2019: 6 · 2018: 13 · 2017: 17 · 2016: 16 · 2015: 12 · 2014: 17 · 2013: 25 · 2012: 29
- FWCI
- 16.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- interleukin-6, insulin resistance, adipocytes, rosiglitazone, insulin signaling, insulin receptor beta, IRS-1, Akt, ERK1/2, GLUT4, lipogenesis, adipogenesis, SOCS3, type 2 diabetes, 3T3-L1 cells
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Rosiglitazone, Animals, Dose-Response Relationship, Drug, Glucose, Insulin Resistance, Proteins, Repressor Proteins, Transcription Factors, Signal Transduction, Interleukin-6, Up-Regulation, 3T3 Cells, Adipocytes, 3T3-L1 Cells, Thiazolidinediones, Suppressor of Cytokine Signaling Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
