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The role of TNFα and TNF receptors in obesity and insulin resistance
Open accessAbstract
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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“TNF␣ is an important factor contributing to obesity-related insulin resistance (46).”
From Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [46]
In the citing paper
“Evidence indicates that inflammation causes insulin resistance”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [283]
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Metadata
- 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
- 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
- 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
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 ›
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