The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Prevention of fat-induced insulin resistance by salicylate
Open accessAbstract
Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation of a serine kinase cascade involving IKK-beta. To test this hypothesis, we first examined insulin action and signaling in awake rats during hyperinsulinemic-euglycemic clamps after a lipid infusion with or without pretreatment with salicylate, a known inhibitor of IKK-beta. Whole-body glucose uptake and metabolism were estimated using [3-(3)H]glucose infusion, and glucose uptake in individual tissues was estimated using [1-(14)C]2-deoxyglucose injection during the clamp. Here we show that lipid infusion decreased insulin-stimulated glucose uptake and activation of IRS-1-associated PI 3-kinase in skeletal muscle but that salicylate pretreatment prevented these lipid-induced effects. To examine the mechanism of salicylate action, we studied the effects of lipid infusion on insulin action and signaling during the clamp in awake mice lacking IKK-beta. Unlike the response in wild-type mice, IKK-beta knockout mice did not exhibit altered skeletal muscle insulin signaling and action following lipid infusion. In summary, high-dose salicylate and inactivation of IKK-beta prevent fat-induced insulin resistance in skeletal muscle by blocking fat-induced defects in insulin signaling and action and represent a potentially novel class of therapeutic agents for type 2 diabetes.
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“As described above, there is substantial local production of inflammatory mediators in organs affected by insulin resistance.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [67]
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“On the other hand, it seems likely that reduced secretion of pro-inflammatory mediators from adipocytes or activated macrophages of adipose tissue contributes to the effect of weight loss (31,36,65,67,142) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [67]
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“Moreover, the insulin resistance was ameliorated with salicylates, which also protected against insulin resistance in rodents after acute lipid infusion,127 and reversed insulin resistance in people with type 2 diabetes mellitus.128”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [127]
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Metadata
- Authors
- Kim, J. K., Kim, Y.-J., Fillmore, J. J., Chen, Y., Moore, I., Lee, J., Yuan, M., Li, Z. W., Karin, M., Perret, P., Shoelson, S. E., & Shulman, G. I.
- Affiliations
- Howard Hughes Medical Institute (US)
- Yale University (US)
- Joslin Diabetes Center (US)
- University of California San Diego (US)
- Harvard University (US)
- Corresponding author
- Shulman, Gerald I.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2001-08-01
- Volume
- 108
- Issue
- 3
- Pages
- 437-446
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC209353
- OpenAlex
- W2097838137
- Cited by
- 737
- References
- 55
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 11 · 2021: 11 · 2020: 12 · 2019: 15 · 2018: 26 · 2017: 23 · 2016: 29 · 2015: 23 · 2014: 26 · 2013: 30 · 2012: 52
- FWCI
- 14.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- U.S. Public Health Service (P30 DK45735, R01 DK-40936)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, P30DK045735, DK 51729, U24DK059635, U24DK59635, R01 DK-45493, R01 DK051729, R01DK040936, R01 DK-59635)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin resistance, salicylates, IKKβ, type 2 diabetes, lipid infusion, skeletal muscle glucose uptake, IRS-1, PI3-kinase, insulin signaling, hyperinsulinemic-euglycemic clamp
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Dietary Fats, Enzyme Inhibitors, Glucose, Infusions, Intravenous, Insulin Resistance, Lipids, Male, Glucose Clamp Technique, Signal Transduction, Rats, Wistar, Protein Serine-Threonine Kinases, Muscle, Skeletal, Salicylic Acid, Rats, I-kappa B Kinase
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