Interleukin-6 induces cellular insulin resistance in hepatocytes.

Senn, Joseph J.; Klover, Peter J.; Nowak, Irena A.; Mooney, Robert A.

doi:10.2337/diabetes.51.12.3391

Cited by 883Adipokines, Inflammation, and Metabolic DiseasesCytokine Signaling Pathways and InteractionsMetabolism, Diabetes, and Cancer

Interleukin-6 induces cellular insulin resistance in hepatocytes.

Open access

Senn, Joseph J., Klover, Peter J., Nowak, Irena A., Mooney, Robert A.·2002·Diabetes

DOI 10.2337/diabetes.51.12.3391

Open this paper in CoChat — free account Open PDF

Abstract

Interleukin (IL)-6 is one of several proinflammatory cytokines that have been associated with insulin resistance and type 2 diabetes. A two- to threefold elevation of circulating IL-6 has been observed in these conditions. Nonetheless, little evidence supports a direct role for IL-6 in mediating insulin resistance. Here, we present data that IL-6 can inhibit insulin receptor (IR) signal transduction and insulin action in both primary mouse hepatocytes and the human hepatocarcinoma cell line, HepG2. This inhibition depends on duration of IL-6 exposure, with a maximum effect at 1-1.5 h of pretreatment with IL-6 in both HepG2 cells and primary hepatocytes. The IL-6 effect is characterized by a decreased tyrosine phosphorylation of IR substrate (IRS)-1 and decreased association of the p85 subunit of phosphatidylinositol 3-kinase with IRS-1 in response to physiologic insulin levels. In addition, insulin-dependent activation of Akt, important in mediating insulin's downstream metabolic actions, is markedly inhibited by IL-6 treatment. Finally, a 1.5-h preincubation of primary hepatocytes with IL-6 inhibits insulin-induced glycogen synthesis by 75%. These data suggest that IL-6 plays a direct role in insulin resistance at the cellular level in both primary hepatocytes and HepG2 cell lines and may contribute to insulin resistance and type 2 diabetes.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.2337/diabetes.51.12.3391

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

IL-6 promotes hepatic insulin resistance through IL-6/STAT3-induced inhibition of insulin receptor signaling.
“consistent with previous studies that indicate IL-6 promotes hepatic insulin resistance through IL-6/STAT3induced inhibition of insulin receptor signaling 18,45,46”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [45]
The Abstract and Discussion report that IL-6 inhibits insulin-receptor signaling and insulin action in hepatocytes. The primary-hepatocyte experiments also show IL-6-induced STAT3 phosphorylation, but use it to assess responsiveness to IL-6; they do not establish that STAT3 causes the inhibition. The Discussion describes a proposed SOCS-mediated mechanism as unproven. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Il6, Spp1, and Igfbp1 are involved in hepatic insulin resistance.
“genes reported to be involved in hepatic insulin resistance, including Il6 45-48 , Spp1 49,50 and Igfbp1 51”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [45]
In cultured hepatocytes, preadipocytes, and mature adipocytes, IL-6 directly impairs insulin action.
“In cultured hepatocytes (25)(26)(27)(28), preadipocytes, and mature adipocytes (29), IL-6 directly impairs insulin action.”
From Signaling Specificity of Interleukin-6 Action on Glucose and Lipid Metabolism in Skeletal Muscle (2006) · cites this paper as [27]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
C-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus
Pradhan, A. D. (2001) · JAMA · doi:10.1001/jama.286.3.327 · Cited by 4,433 · see citing works
IRS-1-Mediated Inhibition of Insulin Receptor Tyrosine Kinase Activity in TNF-α- and Obesity-Induced Insulin Resistance
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 · see citing works
Protection from obesity-induced insulin resistance in mice lacking TNF-α function
Uysal, K. T., Wiesbrock, S. M., Marino, M. W., & Hotamisligil, G. S. (1997) · Nature · doi:10.1038/39335 · Cited by 2,234 · see citing works
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 · see citing works
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 2,012 · see citing works
Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of <i>Ikkβ</i>
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884 · see citing works
Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance
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 · see citing works
NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X
Pickup, J. C., Mattock, M. B., Chusney, G. D., & Burt, D. J. (1997) · Diabetologia · doi:10.1007/s001250050822 · Cited by 1,241 · see citing works
Interleukin-6-deficient mice develop mature-onset obesity
Wallenius, V., Wallenius, K., Ahrén, B., Rudling, M., Carlsten, H., Dickson, S. L., Ohlsson, C., & Jansson, J.-O. (2002) · Nature Medicine · doi:10.1038/nm0102-75 · Cited by 1,213 · see citing works
Tumor necrosis factor alpha inhibits signaling from the insulin receptor.
Hotamışlıgil, G. S., Murray, D. L., Choy, L., & Spiegelman, B. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.11.4854 · Cited by 1,206 · see citing works
Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action
Aguirre, V., Werner, E. D., Giraud, J., Lee, Y. H., Shoelson, S. E., & White, M. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m101521200 · Cited by 1,010 · see citing works
Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha.
Hotamisligil, G. S., Budavari, A., Murray, D., & Spiegelman, B. M. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117495 · Cited by 819 · see citing works
Prevention of fat-induced insulin resistance by salicylate
Kim, J. K., Kim, Y.-J., Fillmore, J. J., Chen, Y., Moore, I., Lee, J., Yuan, M., Li, Z. W., Karin, M., Perret, P., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11559 · Cited by 737 · see citing works
Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor- , in Vivo
Mohamed-Ali, V. (1997) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.12.4196 · Cited by 717 · see citing works
Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways
Rui, L., Aguirre, V., Kim, J. K., Shulman, G. I., Lee, A., Corbould, A. M., Dunaif, A. E., & White, M. F. (2001) · Journal of Clinical Investigation · doi:10.1172/jci10934 · Cited by 600 · see citing works
Muscle‐derived interleukin‐6: possible biological effects
Pedersen, B. K., Steensberg, A., & Schjerling, P. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0329c.xd · Cited by 599 · see citing works
Plasma interleukin-6, tumour necrosis factor α and blood cytokine production in type 2 diabetes
Pickup, J. C., Chusney, G. D., Thomas, S. M., & Burt, D. (2000) · Life Sciences · doi:10.1016/s0024-3205(00)00622-6 · Cited by 566 · cited 2× · see citing works
“Of these proinflammatory cytokines, IL-6 has been shown to have the strongest correlation with insulin resistance and type 2 diabetes (5,9,10).”
Background
Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates.
Feinstein, R., Kanety, H., Papa, M. Z., Lunenfeld, B., & Karasik, A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74276-8 · Cited by 550 · see citing works
Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle
Perreault, M., & Marette, A. (2001) · Nature Medicine · doi:10.1038/nm1001-1138 · Cited by 540 · see citing works
Amino Acid and Insulin Signaling via the mTOR/p70 S6 Kinase Pathway
Tremblay, F., & Marette, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106703200 · Cited by 536 · see citing works
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 · see citing works
SOCS: physiological suppressors of cytokine signaling
Krebs, D. L., & Hilton, D. J. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.16.2813 · Cited by 463 · see citing works
SOCS-3 Inhibits Insulin Signaling and Is Up-regulated in Response to Tumor Necrosis Factor-α in the Adipose Tissue of Obese Mice
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 · see citing works
Mouse liver cell culture
Klaunig, J. E., Goldblatt, P. J., Hinton, D. E., Lipsky, M. M., Chacko, J., & Trump, B. F. (1981) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02618288 · Cited by 404 · see citing works
Dose-Dependent Effects of Recombinant Human Interleukin-6 on Glucose Regulation
Tsigos, C., Papanicolaou, D. A., Kyrou, I., Defensor, R., Mitsiadis, C. S., & Chrousos, G. P. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4422 · Cited by 324 · cited 2× · see citing works
“IL-6 has been shown to increase blood glucose through elevated hepatic glucose output (15,16).”
Background
Serine/threonine phosphorylation of insulin receptor substrate 1 modulates insulin receptor signaling.
Tanti, J., Grémeaux, T., OBBERGHEN, E. V., & MARCHAND‐BRUSTEL, Y. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37568-3 · Cited by 309 · see citing works
Suppressors of Cytokine Signaling-1 and -6 Associate with and Inhibit the Insulin Receptor
Mooney, R. A., Senn, J. J., Cameron, S. J., Inamdar, N. M., Boivin, L. M., Shang, Y., & Furlanetto, R. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010579200 · Cited by 282 · see citing works
Self-citation
Targeted Disruption of the Tumor Necrosis Factor-α Gene: Metabolic Consequences in Obese and Nonobese Mice
Ventre, J. R., Doebber, T. W., Wu, M. S., MacNaul, K. L., Stevens, K. A., Pasparakis, M., Kollias, G. A., & Moller, D. E. (1997) · Diabetes · doi:10.2337/diab.46.9.1526 · Cited by 275 · see citing works
The cancer anorexia-cachexia syndrome.
Nelson, K. A., Walsh, D., & Sheehan, F. (1994) · Journal of Clinical Oncology · doi:10.1200/jco.1994.12.1.213 · Cited by 265 · see citing works
Analysis of liver regeneration in mice lacking type 1 or type 2 tumor necrosis factor receptor: Requirement for type 1 but not type 2 receptor
Yamada, Y., Webber, E. M., Kirillova, I., Peschon, J. J., & Fausto, N. (1998) · Hepatology · doi:10.1002/hep.510280410 · Cited by 260 · see citing works
Insulin resistance and inflammation in an evolutionary perspective: the contribution of cytokine genotype/phenotype to thriftiness
Fernández‐Real, J. M., & Ricart, W. (1999) · Diabetologia · doi:10.1007/s001250051451 · Cited by 247 · see citing works
Interleukin-6 gene polymorphism and insulin sensitivity.
Fernández‐Real, J. M., Broch, M., Vendrell, J. J., Gutiérrez, C., Casamitjana, R., Pugeat, M., Richart, C., & Ricart, W. (2000) · Diabetes · doi:10.2337/diabetes.49.3.517 · Cited by 244 · see citing works
TNF-α impairs insulin signaling and insulin stimulation of glucose uptake in C2C12muscle cells
Aguila, L. F. D., Claffey, K. P., & Kirwan, J. P. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.5.e849 · Cited by 235 · see citing works
Signal Transducer and Activator of Transcription (Stat)-Induced Stat Inhibitor 1 (Ssi-1)/Suppressor of Cytokine Signaling 1 (Socs1) Inhibits Insulin Signal Transduction Pathway through Modulating Insulin Receptor Substrate 1 (Irs-1) Phosphorylation
Kawazoe, Y., Naka, T., Fujimoto, M., Kohzaki, H., Morita, Y., Narazaki, M., Okumura, K., Saitoh, H., Nakagawa, R., Uchiyama, Y., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.2.263 · Cited by 160 · see citing works
Expression of suppressors of cytokine signaling during liver regeneration
Campbell, J. S., Prichard, L., Schaper, F., Schmitz, J., Stephenson-Famy, A., Rosenfeld, M. E., Argast, G. M., Heinrich, P. C., & Fausto, N. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11867 · Cited by 156 · cited 1× · see citing works
“Interestingly, recent evidence suggests that some of the observed effects of TNF- may be mediated by its ability to induce IL-6 and IL-6 receptor expression in tissues such as the liver and muscle (38,39).”
Background
An in Vivo Model for Elucidation of the Mechanism of Tumor Necrosis Factor-α (TNF-α)-Induced Insulin Resistance: Evidence for Differential Regulation of Insulin Signaling by TNF-α
Cheung, A., Ree, D., Kolls, J. K., Fuselier, J. A., Coy, D. H., & Bryer‐Ash, M. (1998) · Endocrinology · doi:10.1210/endo.139.12.6336 · Cited by 153 · see citing works
Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase in human skeletal muscle
Aguila, L. F. D., Krishnan, R. K., Ulbrecht, J. S., Farrell, P. A., Correll, P. H., Lang, C. H., Zierath, J. R., & Kirwan, J. P. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.1.e206 · Cited by 135 · see citing works
Perceived symptoms of hypoglycaemia in elderly Type 2 diabetic patients treated with insulin
Jaap, A. J., Jones, G. C., McCrimmon, R. J., Deary, I. J., & Frier, B. M. (1998) · Diabetic Medicine · doi:10.1002/(sici)1096-9136(199805)15:5 · Cited by 134 · see citing works
Interleukin 1β and interleukin 6, but not tumor necrosis factor α, inhibit insulin-stimulated glycogen synthesis in rat hepatocytes
Kanemaki, T., Kitade, H., Kaibori, M., Sakitani, K., 平松, 義., Kamiyama, Y., Ito, S., & Okumura, T. (1998) · Hepatology · doi:10.1002/hep.510270515 · Cited by 132 · see citing works
Interleukin-6 Enhances Glucose Transport in 3T3-L1 Adipocytes
Stouthard, J. M. L., Elferink, R. P. J. O., & Sauerwein, H. P. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0389 · Cited by 116 · see citing works
Growth Hormone Induces Cellular Insulin Resistance by Uncoupling Phosphatidylinositol 3-Kinase and Its Downstream Signals in 3T3-L1 Adipocytes
Takano, A., Haruta, T., Iwata, M., Usui, I., Uno, T., Kawahara, J., Ueno, E., Sasaoka, T., & Kobayashi, M. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1891 · Cited by 110 · see citing works
Tumor necrosis factor-alpha induces hepatic insulin resistance in obese Zucker (fa/fa) rats via interaction of leukocyte antigen-related tyrosine phosphatase with focal adhesion kinase.
Cheung, A. T., Wang, J., Ree, D., Kolls, J. K., & Bryer‐Ash, M. (2000) · Diabetes · doi:10.2337/diabetes.49.5.810 · Cited by 92 · see citing works
Targeted disruption of the tumor necrosis factor-alpha gene: metabolic consequences in obese and nonobese mice
Ventre, J., Doebber, T. W., Wu, M., MacNaul, K., Stevens, K., Pasparakis, M., Kollias, G. A., & Moller, D. E. (1997) · Diabetes · doi:10.2337/diabetes.46.9.1526 · Cited by 82 · see citing works
IL-6 is essential in TNF-α-induced fever
Sundgren‐Andersson, A. K., Östlund, P., & Bartfai, T. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.6.r2028 · Cited by 69 · see citing works
Augmented Production of Tumor Necrosis Factor-α in Obese Mice
Yamakawa, T., Tanaka, S., Yamakawa, Y., Kiuchi, Y., Isoda, F., Kawamoto, S., Okuda, K., & Sekihara, H. (1995) · Clinical Immunology and Immunopathology · doi:10.1006/clin.1995.1052 · Cited by 68 · see citing works
Compartmentalization and Insulin-Induced Translocations of Insulin Receptor Substrates, Phosphatidylinositol 3-Kinase, and Protein Kinase B in Rat Liver**This work was supported by grants from the Medical Research Council and from the National Cancer Institute of Canada, and by the Cleghorn Fund at McGill University and the M. Pollack Foundation of Montreal.
Balbis, A., Baquiran, G., Bergeron, J. J. M., & Posner, B. I. (2000) · Endocrinology · doi:10.1210/endo.141.11.7774 · Cited by 35 · see citing works
FACTORS INFLUENCING THE EFFECT OF THE SOLUBLE IL-6 RECEPTOR ON IL-6 RESPONSES IN HepG2 HEPATOCYTES
Paysant, J., Blanqué, R., Vasse, M., Soria, C., Soria, J., & Gardner, C. R. (2000) · Cytokine · doi:10.1006/cyto.1999.0649 · Cited by 23 · see citing works
Cytokine-mediated differential induction of hepatic activator protein-1 genes
Wang, S., & Evers, B. M. (1998) · Surgery · doi:10.1016/s0039-6060(98)70257-0 · Cited by 8 · see citing works
Making sense of oxygen sensing
Hardin, C. D. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.t01-1-00002.x · Cited by 3 · see citing works

Flagged first, then by citations

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 · see citing works
Inflammation: the link between insulin resistance, obesity and diabetes
Dandona, P. (2004) · Trends in Immunology · doi:10.1016/j.it.2003.10.013 · Cited by 2,170 · see citing works
Adipose tissue as an endocrine organ
Galić, S., Oakhill, J. S., & Steinberg, G. R. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.08.018 · Cited by 1,597 · see citing works
Visceral fat adipokine secretion is associated with systemic inflammation in obese humans
Fontana, L., Eagon, J. C., Trujillo, M. E., Scherer, P. E., & Klein, S. (2007) · Diabetes · doi:10.2337/db06-1656 · Cited by 1,417 · see citing works
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 · see citing works
Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies
Manna, P., & Jain, S. K. (2015) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2015.0095 · Cited by 1,167 · see citing works
Interleukin-6 (IL-6) Induces Insulin Resistance in 3T3-L1 Adipocytes and Is, Like IL-8 and Tumor Necrosis Factor-α, Overexpressed in Human Fat Cells from Insulin-resistant Subjects
Rotter, V., Nagaev, I., & Smith, U. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301977200 · Cited by 1,062 · see citing works
Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes
Creely, S. J., McTernan, P. G., Kusminski, C. M., Fisher, F. M., Da Silva, N. F., Khanolkar, M., Evans, M., Harte, A. L., & Kumar, S. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00302.2006 · Cited by 1,043 · see citing works
Adipocyte Death, Adipose Tissue Remodeling, and Obesity Complications
Strissel, K. J., Stancheva, Z., Miyoshi, H., Perfield, J. W., DeFuria, J., Jick, Z., Greenberg, A. S., & Obin, M. S. (2007) · Diabetes · doi:10.2337/db07-0767 · Cited by 1,007 · see citing works
Senescence-messaging secretome: SMS-ing cellular stress
Kuilman, T., & Peeper, D. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2560 · Cited by 909 · see citing works
Insulin resistance: a metabolic pathway to chronic liver disease
Bugianesi, E., McCullough, A. J., & Marchesini, G. (2005) · Hepatology · doi:10.1002/hep.20920 · Cited by 900 · see citing works
Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome
Fernández-Real, J. M., & Ricart, W. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0010 · Cited by 886 · see citing works
Ceramides in insulin resistance and lipotoxicity
Summers, S. A. (2005) · Progress in Lipid Research · doi:10.1016/j.plipres.2005.11.002 · Cited by 852 · see citing works
Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training
Roberts, C. K., Hevener, A. L., & Barnard, R. J. (2012) · Comprehensive physiology · doi:10.1002/cphy.c110062 · Cited by 919 · see citing works
Loss-of-Function Mutation in Toll-Like Receptor 4 Prevents Diet-Induced Obesity and Insulin Resistance
Tsukumo, D. M. L., Carvalho-Filho, M. A., Carvalheira, J. B. C., Prada, P. O., Hirabara, S. M., Schenka, A. A., Araújo, E. P., Vassallo, J., Curi, R., Velloso, L. A., et al. (2007) · Diabetes · doi:10.2337/db06-1595 · Cited by 826 · see citing works
Retracted
Interleukin-6 in acute exercise and training: what is the biological relevance?
Fischer, C. P. (2026) · PubMed · doi:10.22029/eir.2006.1620 · Cited by 817 · see citing works
Adipokines and Insulin Resistance
Rabe, K., Lehrke, M., Parhofer, K. G., & Broedl, U. C. (2008) · Molecular Medicine · doi:10.2119/2008-00058.rabe · Cited by 814 · see citing works
Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes
Scheithauer, T. P. M., Rampanelli, E., Nieuwdorp, M., Vallance, B. A., Verchere, C. B., van Raalte, D. H., & Herrema, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.571731 · Cited by 694 · see citing works
Muscles and their myokines
Pedersen, B. K. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.048074 · Cited by 668 · see citing works
Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease
Fuster, J. J., Ouchi, N., Gokce, N., & Walsh, K. X. (2016) · Circulation Research · doi:10.1161/circresaha.115.306885 · Cited by 669 · see citing works
Adiponectin: action, regulation and association to insulin sensitivity
Lihn, A. S., Pedersen, S. B., & Richelsen, B. (2005) · Obesity Reviews · doi:10.1111/j.1467-789x.2005.00159.x · Cited by 660 · see citing works
Tumor Necrosis Factor-α Induces Skeletal Muscle Insulin Resistance in Healthy Human Subjects via Inhibition of Akt Substrate 160 Phosphorylation
Plomgaard, P., Bouzakri, K., Krogh-Madsen, R., Mittendorfer, B., Zierath, J. R., & Pedersen, B. K. (2005) · Diabetes · doi:10.2337/diabetes.54.10.2939 · Cited by 627 · see citing works
Suppressor of Cytokine Signaling-3 (SOCS-3), a Potential Mediator of Interleukin-6-dependent Insulin Resistance in Hepatocytes
Senn, 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 · see citing works
Self-citation
Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2
Haukeland, J. W., Damås, J. K., Konopski, Z., Løberg, E. M., Haaland, T., Goverud, I. L., Torjesen, P. A., Birkeland, K. I., Bjøro, K., & Aukrust, P. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.02.011 · Cited by 605 · see citing works
A Stress Signaling Pathway in Adipose Tissue Regulates Hepatic Insulin Resistance
Sabio, G., Das, M., Mora, A., Zhang, Z., Jun, J. Y., Ko, H. J., Barrett, T., Kim, J. K., & Davis, R. J. (2008) · Science · doi:10.1126/science.1160794 · Cited by 604 · see citing works
Regulation of adipocytokines and insulin resistance
Faßhauer, M., & Paschke, R. (2003) · Diabetologia · doi:10.1007/s00125-003-1228-z · Cited by 543 · see citing works
Differential Effects of Interleukin-6 and -10 on Skeletal Muscle and Liver Insulin Action In Vivo
Kim, H.-J., Higashimori, T., Park, S.-Y., Choi, H., Dong, J., Kim, Y.-J., Noh, H.-L., Cho, Y.-R., Cline, G., Kim, Y.-B., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.4.1060 · Cited by 534 · see citing works
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 534 · see citing works
Interleukin-6 and Diabetes
Kristiansen, O. P., & Mandrup-Poulsen, T. R. (2005) · Diabetes · doi:10.2337/diabetes.54.suppl_2.s114 · Cited by 525 · see citing works
Obesity and Obesity-Initiated Metabolic Syndrome
Wahba, I. M., & MAK, R. H. K. (2007) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.04071206 · Cited by 518 · see citing works
Obesity, inflammation, and liver cancer
Sun, B., & Karin, M. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.09.020 · Cited by 496 · see citing works
Chronic Exposure to Interleukin-6 Causes Hepatic Insulin Resistance in Mice
Klover, P. J., Zimmers, T. A., Koniaris, L. G., & Mooney, R. A. (2003) · Diabetes · doi:10.2337/diabetes.52.11.2784 · Cited by 488 · see citing works
Self-citation
The systemic nature of CKD
Zoccali, C., Vanholder, R. C., Massy, Z. A., Ortíz, A., Sarafidis, P. A., Dekker, F. W., Fliser, D., Fouque, D. P., Heine, G. H., Jager, K. J., et al. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.52 · Cited by 464 · see citing works
Innate immunity and inflammation in ageing: a key for understanding age-related diseases
Licastro, F., Candore, G., Lio, D., Porcellini, E., Colonna-Romano, G., Franceschi, C., & Caruso, C. (2005) · Immunity & Ageing · doi:10.1186/1742-4933-2-8 · Cited by 453 · see citing works
Insulin resistance in chronic kidney disease: a systematic review
Spoto, B., Pisano, A., & Zoccali, C. (2016) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00340.2016 · Cited by 453 · see citing works
The major inflammatory mediator interleukin-6 and obesity
Éder, K., Baffy, N. J., Falus, A., & Fulop, A. K. (2009) · Inflammation Research · doi:10.1007/s00011-009-0060-4 · Cited by 433 · see citing works
Physical activity and modulation of systemic low-level inflammation
Bruunsgaard, H. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0505247 · Cited by 429 · see citing works
Interleukin-10 Prevents Diet-Induced Insulin Resistance by Attenuating Macrophage and Cytokine Response in Skeletal Muscle
Hong, E., Ko, H. J., Cho, Y.-R., Kim, H., Ma, Z., Yu, T. Y., Friedline, R. H., Kurt‐Jones, E. A., Finberg, R. W., Fischer, M. A., et al. (2009) · Diabetes · doi:10.2337/db08-1261 · Cited by 412 · see citing works
Multi-organ proteomic landscape of COVID-19 autopsies
Nie, X., Qian, L.-J., Sun, R., Huang, B., Dong, X., Xiao, Q., Zhang, Q.-S., Lu, T., Yue, L., Chen, S., et al. (2020) · medRxiv · doi:10.1016/j.cell.2021.01.004 · Cited by 373 · see citing works
Monocytes from type 2 diabetic patients have a pro-inflammatory profile
Giulietti, A., van Etten, E., Overbergh, L., Stoffels, K., Bouillon, R., & Mathieu, C. (2007) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2006.10.007 · Cited by 400 · see citing works
Adipose tissue and adipokines: for better or worse
Guerre-Millo, M. (2004) · Diabetes & Metabolism · doi:10.1016/s1262-3636(07)70084-8 · Cited by 387 · see citing works
Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone
Lagathu, C., Bastard, J.-P., Auclair, M., Maachi, M., Capeau, J., & Caron, M. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.10.013 · Cited by 385 · see citing works
Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis
Grosicki, G. J., Fielding, R. A., & Lustgarten, M. S. (2018) · Calcified Tissue International · doi:10.1007/s00223-017-0345-5 · Cited by 388 · see citing works
AMPK inhibition in health and disease
Viollet, B., Horman, S., Leclerc, J., Lantier, L., Foretz, M., Billaud, M., Giri, S., & Andreelli, F. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2010.488215 · Cited by 383 · see citing works
Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat fed/streptozotocin-induced type 2 diabetic rats
Mahmoud, A. M., Ashour, M. B., Abdel‐Moneim, A., & Ahmed, O. M. (2012) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2012.06.001 · Cited by 376 · see citing works
Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk
Juhan-Vague, I., Alessi, M.-C., Mavri, A., & Morange, P. E. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1046/j.1538-7836.2003.00279.x · Cited by 371 · see citing works
Nutrition-induced ketosis alters metabolic and signaling gene networks in liver of periparturient dairy cows
Loor, J. J., Everts, R. E., Bionaz, M., Dann, H. M., Morin, D. E., Oliveira, R., Rodriguez‐Zas, S. L., Drackley, J. K., & Lewin, H. A. (2007) · Physiological Genomics · doi:10.1152/physiolgenomics.00188.2007 · Cited by 366 · see citing works
The role of interleukins in insulin resistance and type 2 diabetes mellitus
Fève, B., & Bastard, J.-P. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.62 · Cited by 343 · see citing works
Hepatocytes: critical for glucose homeostasis
Klover, P. J., & Mooney, R. A. (2003) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2003.10.002 · Cited by 345 · see citing works
Self-citation
Chronic tissue inflammation and metabolic diseasePreprint
Lee, Y. S., & Olefsky, J. M. (2021) · Genes & Development · doi:10.1101/gad.346312.120 · Cited by 342 · see citing works
Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance
Matthews, V. B., Allen, T. L., Risis, S., Chan, M. H. S., Henstridge, D. C., Watson, N., Zaffino, L. A., Babb, J. R., Boon, J., Meikle, P. J., et al. (2010) · Diabetologia · doi:10.1007/s00125-010-1865-y · Cited by 334 · see citing works
Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease
Stojsavljević, S. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i48.18070 · Cited by 325 · see citing works
Acute IL-6 Treatment Increases Fatty Acid Turnover in Elderly Humans in Vivo and in Tissue Culture in Vitro
Petersen, E. W., Carey, A. L., Sacchetti, M., Steinberg, G. R., Macaulay, S. L., Febbraio, M. A., & Pedersen, B. K. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00257.2004 · Cited by 311 · see citing works
Inflammatory Process in Type 2 Diabetes: The Role of Cytokines
ALEXANDRAKI, K., PIPERI, C., KALOFOUTIS, C., SINGH, J., ALAVERAS, A., & KALOFOUTIS, A. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1372.039 · Cited by 309 · see citing works
Catabolism of aging: is it an inflammatory process?
Roubenoff, R. (2003) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/01.mco.0000068965.34812.62 · Cited by 307 · see citing works
IL-6 signalling pathways and the development of type 2 diabetes
Akbari, M., & Hassan‐Zadeh, V. (2018) · Inflammopharmacology · doi:10.1007/s10787-018-0458-0 · Cited by 304 · see citing works
Metabolic syndrome is an inflammatory disorder: A conspiracy between adipose tissue and phagocytes
Reddy, P., Lent-Schochet, D., Ramakrishnan, N., McLaughlin, M., & Jialal, I. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.06.019 · Cited by 297 · see citing works
Adipo-myokines: two sides of the same coin–mediators of inflammation and mediators of exercise
Raschke, S., & Eckel, J. (2013) · Mediators of Inflammation · doi:10.1155/2013/320724 · Cited by 296 · see citing works
Aging Up-Regulates Expression of Inflammatory Mediators in Mouse Adipose Tissue
Wu, D., Ren, Z., Pae, M., Guo, W., Cui, X., Merrill, A. H., & Meydani, S. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.7.4829 · Cited by 288 · see citing works
PGRN is a Key Adipokine Mediating High Fat Diet-Induced Insulin Resistance and Obesity through IL-6 in Adipose Tissue
Matsubara, T., Mita, A., Minami, K., Hosooka, T., Kitazawa, S., Takahashi, K., Tamori, Y., Yokoi, N., Watanabe, M., Matsuo, E., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.002 · Cited by 286 · see citing works
Modulation of insulin action
Pirola, L., Johnston, A., & OBBERGHEN, E. V. (2004) · Diabetologia · doi:10.1007/s00125-003-1313-3 · Cited by 283 · see citing works
Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease
Qureshi, K. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i26.3540 · Cited by 282 · see citing works
Role of immune cells in obesity induced low grade inflammation and insulin resistance
Asghar, A., & Sheikh, N. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.03.001 · Cited by 275 · see citing works
Interleukin-6 depletion selectively improves hepatic insulin action in obesity.
Klover, P. J., Clementi, A. H., & Mooney, R. A. (2005) · Endocrinology · doi:10.1210/en.2004-1468 · Cited by 273 · see citing works
Self-citation
Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty
Stout, M. B., Justice, J. N., Nicklas, B. J., & Kirkland, J. L. (2017) · Physiology · doi:10.1152/physiol.00012.2016 · Cited by 272 · see citing works
Palmitate, but Not Unsaturated Fatty Acids, Induces the Expression of Interleukin-6 in Human Myotubes through Proteasome-dependent Activation of Nuclear Factor-κB
Weigert, C., Brodbeck, K., Staiger, H., Kausch, C., Machicao, F., Häring, H. U., & Schleicher, E. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312692200 · Cited by 269 · see citing works
Obesity Is a Positive Modulator of IL-6R and IL-6 Expression in the Subcutaneous Adipose Tissue: Significance for Metabolic Inflammation
Sindhu, S. T. A. K., Thomas, R., Kochumon, S., Devarajan, S., Behbehani, K., & Ahmad, R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133494 · Cited by 267 · see citing works
Visceral fat and metabolic inflammation: the portal theory revisited
Item, F., & Konrad, D. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01035.x · Cited by 273 · see citing works
From cytokine to myokine: The emerging role of interleukin-6 in metabolic regulation
Pal, M., Febbraio, M. A., & Whitham, M. (2014) · Immunology & Cell Biology · doi:10.1038/icb.2014.16 · Cited by 258 · see citing works
Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin
Piya, M. K., McTernan, P. G., & Kumar, S. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0498 · Cited by 262 · see citing works
Fat as an Endocrine Organ: Relationship to the Metabolic Syndrome
Hutley, L. J., & Prins, J. B. (2005) · The American Journal of the Medical Sciences · doi:10.1097/00000441-200512000-00005 · Cited by 258 · see citing works
Toll-like receptor-2 is essential for the development of palmitate-induced insulin resistance in myotubes
Senn, J. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.a109.513304 · Cited by 8 · see citing works
Self-citation
The Inflammation and Liver Cancer
Bishayee, A. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-0348-0837-8_16 · Cited by 257 · see citing works
Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients
Saraheimo, M., Teppo, A.-M., Forsblom, C., Fagerudd, J., & Groop, P.-H. (2003) · Diabetologia · doi:10.1007/s00125-003-1194-5 · Cited by 255 · see citing works
The JAK / STAT pathway in obesity and diabetes
Gurzov, E. N., Stanley, W. J., Pappas, E. G., Thomas, H. E., & Gough, D. J. (2016) · FEBS Journal · doi:10.1111/febs.13709 · Cited by 253 · see citing works
Signaling Specificity of Interleukin-6 Action on Glucose and Lipid Metabolism in Skeletal Muscle
Al-Khalili, L., Bouzakri, K., Glund, S., Lönnqvist, F., Koistinen, H. A., & Krook, A. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0490 · Cited by 250 · see citing works
Adipocyte-Derived Hormones, Cytokines, and Mediators
Rondinone, C. M. (2006) · Endocrine · doi:10.1385/endo:29:1:81 · Cited by 246 · see citing works
A Burning Question
Tataranni, P. A., & Ortega, E. (2005) · Diabetes · doi:10.2337/diabetes.54.4.917 · Cited by 239 · see citing works
Insulin resistance: a contributing factor to age-related muscle mass loss?
Guillet, C., & Boirie‌, Y. (2005) · Diabetes & Metabolism · doi:10.1016/s1262-3636(05)73648-x · Cited by 237 · see citing works
Obesity-associated low-grade inflammation in type 2 diabetes mellitus: causes and consequences.
van Greevenbroek, M. M. J., Schalkwijk, C., & Stehouwer, C. D. A. (2013) · PubMed · Cited by 233 · see citing works
Insulin Resistance Accelerates a Dietary Rat Model of Nonalcoholic Steatohepatitis
Ota, T., Takamura, T., Kurita, S., Matsuzawa, N., Kita, Y., Uno, M., Akahori, H., Misu, H., Sakurai, M., Zen, Y., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.10.014 · Cited by 227 · see citing works
Chapter 21 Interleukin‐6 and Insulin Resistance
Kim, J., Bachmann, R. A., & Chen, J. (2009) · Vitamins & Hormones · doi:10.1016/s0083-6729(08)00621-3 · Cited by 224 · see citing works
Obesity, its associated disorders and the role of inflammatory adipokines in companion animals
German, A. J., Ryan, V. H., German, A. C., Wood, I. S., & Trayhurn, P. (2010) · The Veterinary Journal · doi:10.1016/j.tvjl.2010.04.004 · Cited by 221 · see citing works
Metabolic syndrome: an update on diagnostic criteria, pathogenesis, and genetic links
Zafar, U., Khaliq, S., Ahmad, H., Manzoor, S., & Lone, K. P. (2018) · HORMONES · doi:10.1007/s42000-018-0051-3 · Cited by 221 · see citing works
Psoriasis comorbidities
Gottlieb, A. B., Chao, C. C., & Dann, F. J. (2008) · Journal of Dermatological Treatment · doi:10.1080/09546630701364768 · Cited by 219 · see citing works
Interleukin-6 Directly Increases Glucose Metabolism in Resting Human Skeletal Muscle
Glund, S., Deshmukh, A., Long, Y. C., Moller, T., Koistinen, H. A., Caidahl, K., Zierath, J. R., & Krook, A. (2007) · Diabetes · doi:10.2337/db06-1733 · Cited by 219 · see citing works
The role of interleukin‐6 in insulin resistance, body fat distribution and energy balance
Hoene, M., & Weigert, C. (2007) · Obesity Reviews · doi:10.1111/j.1467-789x.2007.00410.x · Cited by 218 · see citing works
Edward F. Adolph Distinguished Lecture: Muscle as an endocrine organ: IL-6 and other myokines
Pedersen, B. K. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00734.2009 · Cited by 214 · see citing works
Serum cytokine and soluble cytokine receptor levels in patients with non‐alcoholic steatohepatitis
Abiru, S., Migita, K., Maeda, Y., Daikoku, M., Ito, M., Ohata, K., Nagaoka, S., Matsumoto, T., Takii, Y., Kusumoto, K., et al. (2005) · Liver International · doi:10.1111/j.1478-3231.2005.01191.x · Cited by 209 · see citing works
Diabetes and Altered Glucose Metabolism with Aging
Kalyani, R. R., & Egan, J. M. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.02.010 · Cited by 209 · see citing works
Dual Role of Interleukin-6 in Regulating Insulin Sensitivity in Murine Skeletal Muscle
Nieto-Vazquez, I., Fernández-Veledo, S., de Alvaro, C., & Lorenzo, M. (2008) · Diabetes · doi:10.2337/db07-1062 · Cited by 209 · see citing works
Retracted
Improvement in insulin resistance and reduction in plasma inflammatory adipokines after weight loss in obese dogs
German, A. J., Hervera, M., Hunter, L., Holden, S. L., Morris, P., Biourge, V. C., & Trayhurn, P. (2009) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2009.07.001 · Cited by 205 · see citing works
Suppressor of Cytokine Signaling 3 Expression and Insulin Resistance in Skeletal Muscle of Obese and Type 2 Diabetic Patients
Rieusset, J., Bouzakri, K., Chevillotte, E., Ricard, N., Jacquet, D., Bastard, J.-P., Laville, M., & Vidal, H. (2004) · Diabetes · doi:10.2337/diabetes.53.9.2232 · Cited by 200 · see citing works
Prevalence of atherosclerotic risk factors and the metabolic syndrome in patients with chronic inflammatory arthritis
Mok, C. C., Ko, G. T. C., Ho, L. Y., Yu, K. L., Chan, P. T., & To, C. H. (2010) · Arthritis Care & Research · doi:10.1002/acr.20363 · Cited by 199 · see citing works
The Portal Theory Supported by Venous Drainage–Selective Fat Transplantation
Rytka, J. M., Wueest, S., Schoenle, E. J., & Konrad, D. (2010) · Diabetes · doi:10.2337/db10-0697 · Cited by 209 · see citing works
Exercise Induced Adipokine Changes and the Metabolic Syndrome
Golbidi, S., & Laher, I. (2014) · Journal of Diabetes Research · doi:10.1155/2014/726861 · Cited by 194 · see citing works
Metabolic inflammation: Connecting obesity and insulin resistance
Dali‐Youcef, N., Mecili, M., Ricci, R., & Andrès, E. (2012) · Annals of Medicine · doi:10.3109/07853890.2012.705015 · Cited by 193 · see citing works
Diabetes-enhanced Inflammation and Apoptosis—Impact on Periodontal Pathology
Graves, D. T., Liu, R., Alikhani, M., Almashat, H., & Trackman, P. C. (2006) · Journal of Dental Research · doi:10.1177/154405910608500103 · Cited by 189 · see citing works
Increased intrahepatic triglyceride is associated with peripheral insulin resistance: in vivo MR imaging and spectroscopy studies
Hwang, J.-H., Stein, D. T., Barzilai, N., Cui, M.-H., Tonelli, J., Kishore, P., & Hawkins, M. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00590.2006 · Cited by 188 · see citing works
Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells
Kranendonk, M. E. G., Visseren, F. L. J., van Herwaarden, J. A., Hoen, E. N. M. N., de Jager, W., Wauben, M. H. M., & Kalkhoven, E. (2014) · Obesity · doi:10.1002/oby.20847 · Cited by 187 · see citing works

Interleukin-6 Induces Cellular Insulin Resistance in
Senn, H. J., Klover, P. J., Nowak, I. A., & Mooney, R. A. (2002)
Self-citation
Chronic Exposure to Interleukin-6 Causes Hepatic Insulin Resistance in Mice
Klover, P. J., Zimmers, T. A., Koniaris, L. G., & Mooney, R. A. (2003) · Diabetes · doi:10.2337/diabetes.52.11.2784 · Cited by 488 · see citing works
Self-citation
Differential Effects of Interleukin-6 and -10 on Skeletal Muscle and Liver Insulin Action In Vivo
Kim, H.-J., Higashimori, T., Park, S.-Y., Choi, H., Dong, J., Kim, Y.-J., Noh, H.-L., Cho, Y.-R., Cline, G., Kim, Y.-B., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.4.1060 · Cited by 534 · see citing works
Aggravation by prostaglandin E2 of interleukin-6-dependent insulin resistance in hepatocytes #
Henkel, J., Neuschäfer‐Rube, F., Pathe‐Neuschäfer‐Rube, A., & Püschel, G. P. (2009) · Hepatology · doi:10.1002/hep.23064 · Cited by 73 · see citing works
Verstärkung der Interleukin-6 (IL-6)-vermittelten hepatischen Insulinresistenz durch Prostaglandin E2 (PGE2)
Henkel, J., Trendelenburg, V., Frede, A., Schanze, N., Pathe‐Neuschäfer‐Rube, A., Neuschäfer‐Rube, F., & Püschel, G. P. (2010) · Zeitschrift für Gastroenterologie · doi:10.1055/s-0029-1246411

Authors: Senn, J. J., Klover, P. J., Nowak, I. A., & Mooney, R. A.
Affiliations: University of Rochester Medicine (US)
ORCID: Mooney, Robert A.
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2002-12-01
Volume: 51
Issue: 12
Pages: 3391-3399
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.51.12.3391
OpenAlex: W2130078845
Cited by: 883
References: 51
Citations by year: 2026: 27 · 2025: 19 · 2024: 22 · 2023: 29 · 2022: 28 · 2021: 41 · 2020: 42 · 2019: 31 · 2018: 31 · 2017: 36 · 2016: 49 · 2015: 46 · 2014: 46 · 2013: 34 · 2012: 39
FWCI: 23.00
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: Centers for Disease Control and Prevention (PHS R01 38138)
U.S. Public Health Service
Topics: Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: interleukin-6, insulin resistance, hepatocytes, insulin receptor signaling, IRS-1 tyrosine phosphorylation, phosphatidylinositol 3-kinase, p85 regulatory subunit, Akt activation, glycogen synthesis, type 2 diabetes, inflammatory cytokines
MeSH terms: Animals, Cell Line, Dose-Response Relationship, Drug, Humans, Insulin, Insulin Resistance, Phosphoproteins, Phosphorylation, Proto-Oncogene Proteins, Receptor, Insulin, Time Factors, Tyrosine, Signal Transduction, Interleukin-6, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Hepatocytes, Proto-Oncogene Proteins c-akt, Mice, Insulin Receptor Substrate Proteins

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

Interleukin-6 induces cellular insulin resistance in hepatocytes.

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks