Cited by 819Adipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism

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Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha.

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Hotamisligil, G S, Budavari, A, Murray, D, Spiegelman, B M·1994·Journal of Clinical Investigation

DOI 10.1172/jci117495PMC PMC295304

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Abstract

Insulin resistance is an important metabolic abnormality often associated with infections, cancer, obesity, and especially non-insulin-dependent diabetes mellitus (NIDDM). We have previously demonstrated that tumor necrosis factor-alpha produced by adipose tissue is a key mediator of insulin resistance in animal models of obesity-diabetes. However, the mechanism by which TNF-alpha interferes with insulin action is not known. Since a defective insulin receptor (IR) tyrosine kinase activity has been observed in obesity and NIDDM, we measured the IR tyrosine kinase activity in the Zucker (fa/fa) rat model of obesity and insulin resistance after neutralizing TNF-alpha with a soluble TNF receptor (TNFR)-lgG fusion protein. This neutralization resulted in a marked increase in insulin-stimulated autophosphorylation of the IR, as well as phosphorylation of insulin receptor substrate 1 (IRS-1) in muscle and fat tissues of the fa/fa rats, restoring them to near control (lean) levels. In contrast, no significant changes were observed in insulin-stimulated tyrosine phosphorylations of IR and IRS-1 in liver. The physiological significance of the improvements in IR signaling was indicated by a concurrent reduction in plasma glucose, insulin, and free fatty acid levels. These results demonstrate that TNF-alpha participates in obesity-related systemic insulin resistance by inhibiting the IR tyrosine kinase in the two tissues mainly responsible for insulin-stimulated glucose uptake: muscle and fat.

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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
Short-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues
Raza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,311
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
Self-citation
Elective induction versus spontaneous labor after sonographic diagnosis of fetal macrosomia.
Combs, C. A., Singh, N. B., & Khoury, J. C. (1993) · PubMed · Cited by 2,463
The insulin signaling system.
White, M. F., & Kahn, C. R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42297-6 · Cited by 1,707
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
Sun, X. J., Rothenberg, P., Kahn, C. R., Backer, J. M., Araki, E., Wilden, P. A., Cahill, D. A., Goldstein, B. J., & White, M. F. (1991) · Nature · doi:10.1038/352073a0 · Cited by 1,574
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 1,220
Self-citation
Insulin Stimulates the Phosphorylation of the 95,000-Dalton Subunit of Its Own Receptor
Kasuga, M., Karlsson, F. A., & Kahn, C. R. (1982) · Science · doi:10.1126/science.7031900 · Cited by 1,132
Insulin Resistance — Mechanisms, Syndromes, and Implications
Epstein, F. H., Moller, D. E., & Flier, J. S. (1991) · New England Journal of Medicine · doi:10.1056/nejm199109263251307 · Cited by 807
Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells
White, M. F., Maron, R., & Kahn, C. R. (1985) · Nature · doi:10.1038/318183a0 · Cited by 642

Show all 29 references

Research works printed but not linked: 3

Moller, D. E. 1993. Insulin Resistance. John Wiley and Sons Ltd., UK.
Hotamisligil, G. S., D. L. Murray, L. N. Choy, and B. M. Spiegelman. 1994. TNF-a inhibits signaling from insulin receptor. Proc. Natl. Acad. Sci. USA. 91:4854-4858.
Cotran, R. S., V. Kumar, and S. L. Robbins, editors. 1989. Pathological Basis of Disease. 4th edition. W.B. Saunders Company, Philadelphia, PA. 22- 23.

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Untitled work
(2008) · PubMed · Cited by 84
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Nonalcoholic fatty liver disease and type 2 diabetes: pathophysiological mechanisms shared between the two faces of the same coin
Acierno, C., Caturano, A., Pafundi, P. C., Nevola, R., Adinolfi, L. E., & Sasso, F. C. (2020) · Exploration of Medicine · doi:10.37349/emed.2020.00019 · Cited by 81
Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver disease?
Scalera, A., & Tarantino, G. (2014) · PubMed Central · doi:10.3748/wjg.v20.i28.9217 · Cited by 72
MECHANISMS IN ENDOCRINOLOGY: Metabolic and inflammatory pathways on the pathogenesis of type 2 diabetes
Coope, A., Torsoni, A. S., & Velloso, L. A. (2016) · European Journal of Endocrinology · doi:10.1530/eje-15-1065 · Cited by 73
The stressful condition as a nutritionally dependent adaptive dichotomy
Ingenbleek, Y., & Bernstein, L. H. (1999) · Nutrition · doi:10.1016/s0899-9007(99)00009-x · Cited by 73
Tumor Necrosis Factor‐α Stimulates Cell Proliferation in Adipose Tissue‐Derived Stromal‐Vascular Cell Culture: Promotion of Adipose Tissue Expansion by Paracrine Growth Factors
Kras, K. M., Hausman, D. B., & Martin, R. J. (2000) · Obesity Research · doi:10.1038/oby.2000.20 · Cited by 70
Tissue‐specific effects of in vivo adenosine receptor blockade on glucose uptake in Zucker rats
Crist, G. H., Xu, B., LaNoue, K. F., & Lang, C. H. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.13.1301 · Cited by 70
Interaction between hepatitis C virus and metabolic factors
Kawaguchi, Y. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i11.2888 · Cited by 69
Hepatitis C infection and diabetes
Noto, H., & Raskin, P. (2006) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2006.01.001 · Cited by 69
METABOLIC COMPLICATIONS OF OBESITY
Sheehan, M. T., & Jensen, M. D. (2000) · Medical Clinics of North America · doi:10.1016/s0025-7125(05)70226-1 · Cited by 68
The effect of acute, chronic, and prenatal ethanol exposure on insulin sensitivity.
Ting, J. W., & Lautt, W. (2006) · Pharmacology and Therapeutics · doi:10.1016/j.pharmthera.2005.10.004 · Cited by 70
Effect of tumor necrosis factor-alpha on insulin action in cultured rat skeletal muscle cells
Begum, N., & Ragolia, L. (1996) · Endocrinology · doi:10.1210/endo.137.6.8641197 · Cited by 67
TNF-α Downregulation Modifies Insulin Receptor Substrate 1 (IRS-1) in Metabolic Signaling of Diabetic Insulin-Resistant Hepatocytes
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Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats
Ding, S.-Y., Shen, Z., Chen, Y.-T., Sun, S., Liu, Q., & Xie, M. (2005) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2005.00090.x · Cited by 67
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Sakurai, T., Ogasawara, J., Shirato, K., Izawa, T., Oh‐ishi, S., Ishibashi, Y., Radak, Z. O., Ohno, H., & Kizaki, T. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/9410954 · Cited by 69
Mechanism by which arylamine N -acetyltransferase 1 ablation causes insulin resistance in mice
Camporez, J. P., Wang, Y., Faarkrog, K., Chukijrungroat, N., Petersen, K. F., & Shulman, G. I. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716990115 · Cited by 67
Endotoxin-induced alteration in the expression of leptin and β3-adrenergic receptor in adipose tissue
Berkowitz, D. E., Brown, D., Lee, K. M., Emala, C. W., Palmer, D. J., An, Y., & Breslow, M. J. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.6.e992 · Cited by 66
Impact of adiposity and plasma adipocytokines on diabetic angiopathies in Japanese Type 2 diabetic subjects
Matsuda, M., Kawasaki, F., Yamada, K., Kanda, Y., Saito, M., Eto, M., Matsuki, M., & Kaku, K. (2004) · Diabetic Medicine · doi:10.1111/j.1464-5491.2004.01261.x · Cited by 65
Free fatty acids – do they play a central role in type 2 diabetes?
Arner, P. (2001) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2001.00031.x · Cited by 67
Inhibition of insulin receptor signaling by TNF: Potential role in obesity and non-insulin-dependent diabetes mellitus
Skolnik, E. Y., & Marcusohn, J. (1996) · Cytokine & Growth Factor Reviews · doi:10.1016/1359-6101(96)00021-4 · Cited by 65
Insulin resistance in fat cells from obese Zucker rats - Evidence for an impaired activation and translocation of protein kinase B and glucose transporter 4
Carvalho, E., Rondinone, C. M., & Smith, U. (2000) · Molecular and Cellular Biochemistry · doi:10.1023/a:1007009723616 · Cited by 65
β-adrenoceptor agonists downregulate adiponectin, but upregulate adiponectin receptor 2 and tumor necrosis factor-α expression in adipocytes
Fu, L., Isobe, K., Zeng, Q., Suzukawa, K., Takekoshi, K., & Kawakami, Y. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.05.005 · Cited by 67
Adipose tissue, immune aging, and cellular senescence
Frasca, D., & Blomberg, B. B. (2020) · Seminars in Immunopathology · doi:10.1007/s00281-020-00812-1 · Cited by 72
Accumulation of LDL in Rat Arteries Is Associated With Activation of Tumor Necrosis Factor-α Expression
Niemann-Jönsson, A., Dimayuga, P. C., Jovinge, S. V., Calara, F., Ares, M. P. S., Fredrikson, G. N., & Nilsson, J. Å. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.10.2205 · Cited by 65
Hidradenitis suppurativa and diabetes mellitus: updated systematic review and adjusted meta‐analysis
Phan, K. H., Charlton, O., & Smith, S. D. (2019) · Clinical and Experimental Dermatology · doi:10.1111/ced.13922 · Cited by 61
Prevalence of type 2 diabetes mellitus among patients with hidradenitis suppurativa in the United States
Garg, A., Birabaharan, M., & Strunk, A. (2018) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2018.01.014 · Cited by 61
Periodontal, metabolic, and cardiovascular disease: Exploring the role of inflammation and mental health
Makkar, H., Reynolds, M. A., Wadhawan, A., Dagdag, A., Merchant, A. T., & Postolache, T. T. (2018) · Pteridines · doi:10.1515/pteridines-2018-0013 · Cited by 66
The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections
Hornung, F., Rogal, J., Loskill, P., Löffler, B., & Deinhardt‐Emmer, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073456 · Cited by 63

Authors: Hotamisligil, G. S., Budavari, A., Murray, D., & Spiegelman, B. M.
Affiliations: Harvard University (US)
ORCID: Spiegelman, B M
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1994-10-01
Volume: 94
Issue: 4
Pages: 1543-1549
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci117495
PMC: PMC295304
OpenAlex: W2053200285
Cited by: 819
References: 29
Citations by year: 2026: 8 · 2025: 20 · 2024: 14 · 2023: 13 · 2022: 23 · 2021: 22 · 2020: 26 · 2019: 15 · 2018: 26 · 2017: 20 · 2016: 25 · 2015: 31 · 2014: 24 · 2013: 39 · 2012: 30
FWCI: 21.22
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Joslin Diabetes Center
National Institutes of Health (5r01dk042539-08)
Genentech
National Institute of Diabetes and Digestive and Kidney Diseases (DK42539)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: insulin receptor tyrosine kinase, insulin resistance, TNF-α, obesity, type 2 diabetes, IRS-1, soluble TNF receptors, adipose tissue, skeletal muscle, adipocytes, glucose uptake, free fatty acids, plasma glucose, insulin, Zucker fatty rats
MeSH terms: Adipose Tissue, Animals, Diabetes Mellitus, Diabetes Mellitus, Type 2, Disease Models, Animal, Immunoglobulin G, Insulin, Insulin Resistance, Liver, Male, Muscles, Neutralization Tests, Obesity, Phosphoproteins, Phosphorylation, Protein-Tyrosine Kinases, Rats, Zucker, Receptor, Insulin, Recombinant Fusion Proteins, Specific Pathogen-Free Organisms, Tumor Necrosis Factor-alpha, Tyrosine, Receptors, Tumor Necrosis Factor, Phosphotyrosine, Rats, Insulin Receptor Substrate Proteins

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Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha.

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