Cited by 783Adipokines, Inflammation, and Metabolic DiseasesDiabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and Cancer

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The role of TNFα and TNF receptors in obesity and insulin resistance

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Hotamisligil, G. S.·1999·Journal of Internal Medicine

DOI 10.1046/j.1365-2796.1999.00490.x

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Abstract

Abstract. Hotamisligil GS (Harvard University, Boston, Massachusetts, USA). The role of TNFα and TNF receptors in obesity and insulin resistance. (Minisymposium: Genes & Obesity). J Intern Med 1999; 245: 621–625. Insulin resistance, a smaller than expected response to a given dose of insulin, is associated with many common diseases including, ageing, polycystic ovarian disease, syndrome X, cancer, infections, trauma and, most significantly, obesity and type 2 diabetes mellitus. The biochemical basis of insulin resistance in type 2 diabetes has been the subject of many studies. Earlier studies have indicated that quantitative regulation of the insulin sensitive glucose transporters (Glut‐4) and insulin receptors themselves may contribute to this disorder, however, these two factors are probably inadequate to explain the extent of insulin resistance. This point also became apparent by the development of only mild hyperinsulinaemia in mice with a targeted mutation in the Glut‐4 gene. Studies on postreceptor defects in type 2 diabetes has recently focused on the intrinsic catalytic activity of the insulin receptor and downstream signalling events. A reduction in tyrosine phosphorylation of both the insulin receptor (IR) and the insulin receptor substrate‐1 (IRS‐1) has been noted in both animal and human type 2 diabetes. Importantly, this appears to occur in all of the major insulin‐sensitive tissues, namely the muscle, fat and liver. It is now clear that decreased signalling capacity of the insulin receptor is an important component of this disease. I will review some of the potential mechanisms underlying this deficiency.

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Authors: Hotamisligil, G. S.
Venue: Journal of Internal Medicine
Publisher: Wiley
Published: 1999-06
Volume: 245
Issue: 6
Pages: 621-625
ISSN: 0954-6820 (ISSN-L)
1365-2796
DOI: 10.1046/j.1365-2796.1999.00490.x
OpenAlex: W2009818179
Cited by: 780
References: 41
Citations by year: 2026: 5 · 2025: 14 · 2024: 13 · 2023: 9 · 2022: 15 · 2021: 24 · 2020: 7 · 2019: 16 · 2018: 23 · 2017: 25 · 2016: 24 · 2015: 19 · 2014: 25 · 2013: 34 · 2012: 31
FWCI: 6.79
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 938 d)
Locations: Journal of Internal Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: TNF-α, TNF receptor, obesity, insulin resistance, type 2 diabetes, insulin receptor signaling, tyrosine phosphorylation, IRS-1, GLUT4, postreceptor defect
MeSH terms: Animals, Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Mice, Transgenic, Obesity, Tumor Necrosis Factor-alpha, Receptors, Tumor Necrosis Factor, Mice

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The role of TNFα and TNF receptors in obesity and insulin resistance

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