Cited by 431Adipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and CancerNF-κB Signaling Pathways

Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation

Tanti, Jean-François, Jager, Jennifer·2009·Current Opinion in Pharmacology

Abstract

Insulin receptor substrates (IRS) serine phosphorylation is a time-controlled physiological feedback mechanism in insulin signaling that is hijacked by metabolic and inflammatory stresses to promote insulin resistance. Kinases, including IKKbeta, JNK, ERK, mTOR, and S6K, activated by the inducers of insulin resistance induce uncontrolled IRS serine phosphorylation. Studies with genetically modified mice reveal that these kinases integrate signals from metabolic and inflammatory stresses in adipose tissue, liver, and hypothalamus leading to peripheral and central insulin resistance. Moreover, IKKbeta/NF-kappaB and JNK1 pathways in myeloid cells represent a core mechanism involved in inflammation linked to obesity. These kinases are thus potential drug targets against insulin resistance and the targeting of the IKKbeta/NF-kappaB or the JNK pathway may evolve into future diabetes medication.

Integrity signals

Registry

Crossref · 10.1016/j.coph.2009.07.004

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74 of 74 references verified0 citation errors · 0 not checkable

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  • Increased stress kinase activity has been implicated in contributing to serine phosphorylation of IRS-1 and subsequent impairment of tyrosine phosphorylation.

    “Increased stress kinase activity also has been implicated in contribute to the serine phosphorylation of IRS-1 and subsequent impairment tyrosine phosphorylation [177, 178].”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [177]

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Authors
Tanti, J.-F., & Jager, J.
Affiliations
Inserm (FR)
Corresponding author
Tanti, Jean-François
Venue
Current Opinion in Pharmacology
Publisher
Elsevier BV
Published
2009-12
Volume
9
Issue
6
Pages
753-762
ISSN
1471-4892 (ISSN-L)
OpenAlex
W2001649002
Cited by
430
References
74
Citations by year
2026: 19 · 2025: 14 · 2024: 8 · 2023: 17 · 2022: 29 · 2021: 24 · 2020: 17 · 2019: 20 · 2018: 23 · 2017: 28 · 2016: 32 · 2015: 36 · 2014: 41 · 2013: 41 · 2012: 38
FWCI
18.13
Type
journal article
Language
en
Open access
closed
Locations
  • Current Opinion in Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
insulin resistance, insulin receptor substrate, serine phosphorylation, insulin signaling, IKKβ, NF-κB, JNK, ERK, mTOR, S6K, inflammation, obesity, adipose tissue, liver, hypothalamus, myeloid cells
MeSH terms
Animals, Diabetes Mellitus, Type 2, Humans, Inflammation, Insulin Resistance, Models, Biological, Phosphorylation, Signal Transduction, NF-kappa B, Drug Delivery Systems, Protein Serine-Threonine Kinases, Mice, Knockout, Intracellular Signaling Peptides and Proteins, Mice, I-kappa B Kinase, Insulin Receptor Substrate Proteins, TOR Serine-Threonine Kinases

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