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

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Interleukin-6 induces cellular insulin resistance in hepatocytes.

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

DOI 10.2337/diabetes.51.12.3391

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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.

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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
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
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
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
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
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
Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of Ikkβ
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
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
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 1,246

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“[106] Senn JJ, Klover PJ, Nowak IA, et al.”
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Background
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Background
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Grønbæk, H., Thomsen, K. L., Rungby, J., Schmitz, O., & Vilstrup, H. (2008) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2.5.705 · Cited by 44
Leptin, ghrelin, and proinflammatory cytokines: compounds with nutritional impact in chronic kidney disease?
Stenvinkel, P., Pecoits‐Filho, R., & Lindholm, B. (2003) · Advances in Renal Replacement Therapy · doi:10.1053/j.arrt.2003.08.009 · Cited by 42
Vitamin K Contribution to DNA Damage—Advantage or Disadvantage? A Human Health Response
Kaźmierczak-Barańska, J., & Karwowski, B. T. (2022) · Nutrients · doi:10.3390/nu14204219 · Cited by 41
“IL-6 has been implicated in the pathology of a wide range of diseases, including coronary artery disease (CAD) [37], which contributes to diabetes [38], aging [39,40] and cancer progression [41].”
Background
Endothelial function is impaired in HIV-infected patients with lipodystrophy
Masiá, M., Padilla, S., García, N., Jarrín, I., Bernal, E., López, N., Hernández‐Aguado, I., & Gutiérrez, F. (2010) · Antiviral Therapy · doi:10.3851/imp1491 · Cited by 41
“Among its actions, IL-6 also attenuates insulin sensitivity [26] and a reciprocal relationship has been described between insulin resistance and endothelial dysfunction [27,28].”
Background
PANDER binds to the liver cell membrane and inhibits insulin signaling in HepG2 cells
Yang, J., Wang, C., Li, J., Burkhardt, B. R., Robert, C. E., Wilson, C. G., Gao, Z., & Wolf, B. A. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.08.008 · Cited by 41
“The results indicated that the minimal PANDER concentration for significantly inhibiting insulin-stimulated IRS-1 tyrosine phosphorylation within 8 h was 400 pM (about 8 ng/mL), which was comparable to the concentration of other proinflammatory cytokines tested in previous studies [21,28].”
BackgroundMethodResult
Associations between circulating levels of adipocytokines and abdominal adiposity in patients after acute pancreatitis
Singh, R. G., Pendharkar, S. A., Gillies, N. A., Miranda-Soberanis, V., Plank, L. D., & Petrov, M. S. (2017) · Clinical and Experimental Medicine · doi:10.1007/s10238-017-0453-6 · Cited by 41
“Not only do these adipocytokines directly interfere with insulin receptor signalling [21], but they also influence insulin sensitivity indirectly through their stimulation of lipolysis.”
Background
Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice
Ohno, M., Sekiya, T., Nomura, N., Daito, T. J., Shingai, M., & Kida, H. (2020) · Scientific Reports · doi:10.1038/s41598-020-67879-6 · Cited by 41
Insulin resistance in hyperthyroidism: the role of IL6 and TNFα
Mitrou, P., Boutati, E. I., Lambadiari, V., Tsegka, A., Raptis, A. E., Tountas, N. A., Economopoulos, T., Raptis, S., & Dimitriadis, G. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0622 · Cited by 41
β-Klotho promotes glycolysis and glucose-stimulated insulin secretion via GP130
Geng, L., Liao, B., Jin, L., Yu, J., Zhao, X., Zhao, Y., Zhong, L., Wang, B., Li, J., Liu, J., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00572-2 · Cited by 41
Aerobic exercise improves insulin resistance and decreases body fat and serum levels of leptin in patients with hepatitis C virus
Konishi, I., Hiasa, Y., Tokumoto, Y., Abe, M., Furukawa, S., Toshimitsu, K., Matsuura, B., & Onji, M. (2011) · Hepatology Research · doi:10.1111/j.1872-034x.2011.00833.x · Cited by 40
Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes
Sargsyan, A., & Herman, M. A. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1195-5 · Cited by 42
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Zhang, W., Shen, X., Xie, L., Chu, M., & Ma, Y. (2015) · Journal of Inflammation · doi:10.1186/s12950-015-0061-8 · Cited by 40
“The fine tuning of IL-6 expression is crucial since dysregulation of IL-6 has been attributed to many diseases such as atherosclerosis [21], systemic lupus erythematosus [22], Behçet ′s disease [23], diabetes [24], multiple myeloma [25], depression [26], Alzheimer′s Disease [27], prostate cancer [28] and rheumatoid ar…”
Background
Pyrrolidine Dithiocarbamate Inhibits Interleukin-6 Signaling through Impaired STAT3 Activation and Association with Transcriptional Coactivators in Hepatocytes
He, H., Zhu, T. N., Xie, Y., Fan, J., Kole, S., Saxena, S. P., & Bernier, M. (2006) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84049-8 · Cited by 39
Genetic Ablation of cGMP-Dependent Protein Kinase Type I Causes Liver Inflammation and Fasting Hyperglycemia
Lutz, S. Z., Hennige, A. M., Feil, S. C., Peter, A., Gerling, A., Machann, J., Kröber, S. M., Rath, M., Schürmann, A., Weigert, C., et al. (2011) · Diabetes · doi:10.2337/db10-0760 · Cited by 41
“Elevated IL-6 levels cause hepatic insulin resistance both in vitro (36,37) and in vivo (24,38).”
Expression of miRNA in obesity and insulin resistance: a review
Estrella-Ibarra, P., García‐Solís, P., Solís‐S, J. C., & Cruz–Hernández, A. (2021) · Endokrynologia Polska · doi:10.5603/ep.a2021.0002 · Cited by 40
Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity
Civera, M., Urios, A., García-Torres, M. L., Ortega, J., Martínez-Valls, J. F., Fernández, N. C., del Olmo, J. A., Ferrandez, A., Rodrigo, J. M., & Montoliu, C. (2010) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1070 · Cited by 39
“the metabolism and action of insulin [6].”
The Metabolic Syndrome in Systemic Lupus Erythematosus
Parker, B., & Bruce, I. N. (2010) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2009.12.004 · Cited by 39
Short-term infusion of interleukin-6 does not induce insulin resistance in vivo or impair insulin signalling in rats
Sopasakis, V. R., Larsson, B.-M., Johansson, A., Holm�ng, A., & Smith, U. (2004) · Diabetologia · doi:10.1007/s00125-004-1544-y · Cited by 40
“In addition to the large pool of data supporting a role for IL-6 in insulin resistance, as well as directly demonstrating that this cytokine impairs insulin signalling [11, 16, 17, 18], IL-6 ablation in mice has provided evidence for other effects.”
BackgroundInfluential
Myokine Expression in Muscle and Myotubes in Response to Exercise Stimulation
Covington, J. D., Tam, C. S., Bajpeyi, S., Galgani, J. E., Noland, R. C., Smith, S. R., Redman, L. M., & Ravussin, É. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000787 · Cited by 38
Altered Gene and Protein Expressions in Torn Rotator Cuff Tendon Tissues in Diabetic Patients
Chung, S. W., Choi, B. M., Kim, J. Y., Lee, Y., Yoon, J. P., Oh, K.-S., & Park, K. S. (2016) · Arthroscopy The Journal of Arthroscopic and Related Surgery · doi:10.1016/j.arthro.2016.08.017 · Cited by 38
Hepatitis C virus-associated insulin resistance: pathogenic mechanisms and clinical implications
Hung, C., Lee, C., & Lu, S. (2011) · Expert Review of Anti-infective Therapy · doi:10.1586/eri.11.33 · Cited by 38
Pi-Dan-Jian-Qing decoction ameliorates type 2 diabetes mellitus through regulating the gut microbiota and serum metabolism
Xie, X., Liao, J., Ai, Y., Gao, J., Zhao, J., Qu, F., Xu, C., Zhang, Z., Wen, W., Cui, H., et al. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.748872 · Cited by 37
“IL-6 decreases insulin activity by blocking the expression of insulin receptor signaling, leading to the development of IR (Senn et al., 2002).”
Background
Diabetes, insulin resistance, and asthma: a review of potential links
Wu, T. D. (2020) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000738 · Cited by 38
The effect of sodium-glucose co-transporter-2 (SGLT2) inhibitors on blood interleukin-6 concentration: a systematic review and meta-analysis of randomized controlled trials
Gohari, S., Ismail‐Beigi, F., Mahjani, M., Ghobadi, S., Jafari, A., Ahangar, H., & Gohari, S. (2023) · BMC Endocrine Disorders · doi:10.1186/s12902-023-01512-1 · Cited by 39
“IL-6 exacerbates insulin resistance by activating STAT-3 in hepatocytes [40].”
Background
Topically Applied Curcumin-Loaded Nanoparticles Treat Erectile Dysfunction in a Rat Model of Type-2 Diabetes
Draganski, A. R., Tar, M. T., Villegas, G., Friedman, J. M., & Davies, K. P. (2018) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2018.03.009 · Cited by 37
Acute administration of IL-6 improves indices of hepatic glucose and insulin homeostasis in lean and obese mice
Peppler, W. T., Townsend, L. K., Meers, G. M.-E., Panasevich, M. R., MacPherson, R. E. K., Rector, R. S., & Wright, D. C. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00097.2018 · Cited by 37
“Thus, the total exposure to IL-6 was 90 min, which is directly based on prior reports using HepG2 cells (41) and is similar to others (4, 35).”
BackgroundMethodResultInfluential
Understanding the link between insulin resistance and Alzheimer’s disease: Insights from animal models
Silva, N. M. L. E., Gonçalves, R. A., Boehnke, S. E., Forny‐Germano, L., Munoz, D. P., & Felice, F. G. D. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.03.016 · Cited by 37
IL-6 increases muscle insulin sensitivity only at superphysiological levels
Geiger, P. C., Hancock, C., Wright, D. C., Han, D.-H., & Holloszy, J. O. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00701.2006 · Cited by 36
“These include coronary heart disease (CHD)/myocardial infarction (18, 34), congestive heart failure (5), functional disability/frailty in the elderly (4), arterial stiffness (43), and insulin resistance/type 2 diabetes (7, 27, 32, 33, 36, 37).”
Adipose Tissue is Enriched for Activated and Late-Differentiated CD8+ T Cells and Shows Distinct CD8+ Receptor Usage, Compared With Blood in HIV-Infected Persons
Koethe, J. R., McDonnell, W. J., Kennedy, A. J., Abana, C. O., Pilkinton, M. A., Setliff, I., Georgiev, I. S., Barnett, L. D., Hager, C. C., Smith, R. M., et al. (2017) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000001573 · Cited by 36
Serum untargeted metabolomics analysis of the mechanisms of evodiamine on type 2 diabetes mellitus model rats
Yu, Y., Lu, Q., Chen, F., Wang, S., Niu, C., Liao, J., Wang, H., & Chen, F. (2022) · Food & Function · doi:10.1039/d1fo04396j · Cited by 36
Is insulin resistance caused by defects in insulin's target cells or by a stressed mind?
Burén, J., & Eriksson, J. W. (2005) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.567 · Cited by 35
“inhibit insulin receptor signal transduction in hepatocytes has recently been described [54].”
Background
Activation of the GP130-STAT3 axis and its potential implications in nonalcoholic fatty liver disease
Min, H.-K., Mirshahi, F., Verdianelli, A., Pacana, T., Patel, V., Park, C.-G., Choi, A., Lee, J.-H., Park, C.-B., Ren, S., et al. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00390.2014 · Cited by 45
“IL-6, a cytokine known to be increased in obesity and insulin-resistant states (20, 22), is a prototypic gp130 cytokine and activates Janus-activated kinase (JAK)-signal transduction and activator of transcription 3 (JAK-STAT3), Src-Ras, and the phosphatidylinositol 3-kinase-Akt pathways via gp130 (23, 28).”
Background
Understanding MASLD — from molecular pathogenesis to cardiovascular risk: A concise review for the clinical cardiologist
Ratti, C., Malaguti, M., D’Aniello, E., Bellasi, A., & Sanna, G. (2025) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2025.120495 · Cited by 42
Redox proteins are constitutively secreted by skeletal muscle
Manabe, Y., Takagi, M., Yamada, M., Goto‐Inoue, N., Taoka, M., Isobe, T., & FUJII, N. L. (2014) · The Journal of Physiological Sciences · doi:10.1007/s12576-014-0334-7 · Cited by 35
“This is particularly because both positive (increased glucose uptake in myocytes [4] and increased insulin-stimulated glycogen synthesis in skeletal muscle [5]) and negative (reduced insulin sensitivity in skeletal muscle [6], adipocytes [7], and hepatocytes [8]) roles have”
TLR4/NF-κB Signaling Pathway Participates in the Protective Effects of Apocynin on Gestational Diabetes Mellitus Induced Placental Oxidative Stress and Inflammation
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“IL-6 has been shown to inhibit insulin receptor (IR) signal transduction and insulin action in both mouse and the human hepatocytes [27].”
Background
Peanut skin extract ameliorates the symptoms of type 2 diabetes mellitus in mice by alleviating inflammation and maintaining gut microbiota homeostasis
Xiang, L., Wu, Q., Osada, H., Yoshida, M., Pan, W., & Qi, J. (2020) · Aging · doi:10.18632/aging.103521 · Cited by 35
The Association of Acute Phase Proteins in Stress and Inflammation-Induced T2D
Speelman, T., Dale, L., Louw, A., & Verhoog, N. J. D. (2022) · Cells · doi:10.3390/cells11142163 · Cited by 38
Inflammatory cytokines in insulin-treated patients with type 2 diabetes
Mavridis, G., Souliou, E., Diza, E., Symeonidis, G., Pastore, F., Vassiliou, A. M., & Karamitsos, D. T. (2007) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2007.02.013 · Cited by 35
Association of plasma homocysteine with serum interleukin-6 and C-peptide levels in patients with type 2 diabetes
Araki, A., Hosoi, T., Orimo, H., & Ito, H. (2005) · Metabolism · doi:10.1016/j.metabol.2005.02.001 · Cited by 34
Obesity-associated mouse adipose stem cell secretion of monocyte chemotactic protein-1
Zhou, H. R., Kim, E., Kim, H., & Claycombe, K. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00186.2007 · Cited by 35
“STUDIES HAVE SHOWN that obesity-associated increases in circulating proinflammatory cytokine levels decrease with a reduction in body weight, particularly with decreased body adipose tissue mass (4, 10, 34), suggesting adipose tissue is an important source of obesity-associated increases in inflammatory responses.”
Background
Adipocytokines, inflammatory and oxidative stress markers of clinical relevance altered in young overweight/obese subjects
Chielle, E. O., de Souza, W. M., da Silva, T. P., Moresco, R. N., & Moretto, M. B. (2016) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2016.01.003 · Cited by 34
A narrative review on effects of vitamin D on main risk factors and severity of Non-Alcoholic Fatty Liver Disease
Sangouni, A. A., Ghavamzadeh, S., & Jamalzehi, A. (2019) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2019.05.013 · Cited by 34
Obesity‐Related Pulmonary Arterial Hypertension in Rats Correlates with Increased Circulating Inflammatory Cytokines and Lipids and with Oxidant Damage in the Arterial Wall but not with Hypoxia
Irwin, D. C., Garat, C., Crossno, J. T., MacLean, P. S., Sullivan, T. M., Erickson, P. F., Jackman, M. R., Harral, J. W., Reusch, J. E. B., & Klemm, D. J. (2014) · Pulmonary Circulation · doi:10.1086/678510 · Cited by 34
“in peripheral tissues via blockade of the insulin signaling pathway.(56,57) In conjunction with elevated circulating lipids, loss of insulin responsiveness may have a potent impact on arterial cell phenotype via changes in fuel metab-”
Background
The effect of Porphyromonas gingivalis infection on cytokine levels in type 2 diabetic mice
Nishihara, R., Sugano, N., Takano, M., Shimada, T., Tanaka, H., Oka, S., & Ito, K. (2009) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2008.01130.x · Cited by 34
Dietary lipids and gene expression
Roche, H. M. (2004) · Biochemical Society Transactions · doi:10.1042/bst0320999 · Cited by 33

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 › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Immunology and Microbiology › Immunology › 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

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Interleukin-6 induces cellular insulin resistance in hepatocytes.

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