CoChat
Sign Up
Cited by 534Adipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and CancerCytokine Signaling Pathways and Interactions

Differential Effects of Interleukin-6 and -10 on Skeletal Muscle and Liver Insulin Action In Vivo

Open access
Kim, Hyo-Jeong, Higashimori, Takamasa, Park, So-Young, Choi, Hyejeong, Dong, Jianying, Kim, Yoon-Jung, Noh, Hye-Lim, Cho, You-Ree +3 more·2004·Diabetes
DOI 10.2337/diabetes.53.4.1060
Open this paper in CoChat — free accountOpen PDF

Abstract

The circulating level of the inflammatory cytokine interleukin (IL)-6 is elevated in various insulin-resistant states including type 2 diabetes, obesity, cancer, and HIV-associated lipodystrophy. To determine the role of IL-6 in the development of insulin resistance, we examined the effects of IL-6 treatment on whole-body insulin action and glucose metabolism in vivo during hyperinsulinemic-euglycemic clamps in awake mice. Pretreatment of IL-6 blunted insulin’s ability to suppress hepatic glucose production and insulin-stimulated insulin receptor substrate (IRS)-2–associated phosphatidylinositol (PI) 3-kinase activity in liver. Acute IL-6 treatment also reduced insulin-stimulated glucose uptake in skeletal muscle, and this was associated with defects in insulin-stimulated IRS-1–associated PI 3-kinase activity and increases in fatty acyl-CoA levels in skeletal muscle. In contrast, we found that co-treatment of IL-10, a predominantly anti-inflammatory cytokine, prevented IL-6–induced defects in hepatic insulin action and signaling activity. Additionally, IL-10 co-treatment protected skeletal muscle from IL-6 and lipid-induced defects in insulin action and signaling activity, and these effects were associated with decreases in intramuscular fatty acyl-CoA levels. This is the first study to demonstrate that inflammatory cytokines IL-6 and IL-10 alter hepatic and skeletal muscle insulin action in vivo, and the mechanism may involve cytokine-induced alteration in intracellular fat contents. These findings implicate an important role of inflammatory cytokines in the pathogenesis of insulin resistance.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2337/diabetes.53.4.1060

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Interleukin-6 causes hepatic and muscle insulin resistance in humans and in mice.

    “and causes hepatic and muscle insulin resistance in humans and in mice (39,55-60).”

    From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [57]

    The sections on IL-6-induced hepatic insulin resistance and decreased skeletal muscle insulin action report both effects in IL-6-treated mice. The paper does not establish that IL-6 causes hepatic and muscle insulin resistance in humans; its introduction mentions an association between IL-6 gene variants and human insulin sensitivity, not the claimed causal, tissue-specific effects. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Recent studies in rodents have demonstrated that acute infusions of IL-6 cause insulin resistance in both liver and skeletal muscle.

    “Recent studies in rodents have demonstrated that acute infusions of IL-6 caused insulin resistance in both liver and skeletal muscle (32).”

    From Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men (2006) · cites this paper as [32]

  • In contexts of chronically increased IL6 such as obesity or rheumatoid arthritis, IL6 has been shown to induce insulin resistance.

    “In contexts of chronically increased IL6 such as obesity or rheumatoid arthritis, IL6 has been shown to induce insulin resistance (Castaneda et al., 2019; Kim et al., 2004; Perry et al., 2015).”

    From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Kim et al., 2004

  • IL-6 infusion in mice reduces the effect of insulin to suppress hepatic glucose output and reduces insulin-stimulated skeletal muscle glucose uptake.

    “IL-6 infusion in mice has been reported to reduce the effect of insulin to suppress hepatic glucose output and reduce insulin-stimulated skeletal muscle glucose uptake (32), whereas others report no effect of IL-6 on whole-body glucose disposal (33).”

    From Signaling Specificity of Interleukin-6 Action on Glucose and Lipid Metabolism in Skeletal Muscle (2006) · cites this paper as [32]

  • In vitro studies demonstrate that IL-6 can induce insulin resistance in isolated 3T3-L1 adipocytes and in mice.

    “In vitro studies demonstrate that IL-6 can induce insulin resistance in isolated 3T3-L1 adipocytes [51, 52] and in mice [53].”

    From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [53]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kim, H.-J., Higashimori, T., Park, S.-Y., Choi, H., Dong, J., Kim, Y.-J., Noh, H.-L., Cho, Y.-R., Cline, G., Kim, Y.-B., & Kim, J. K.
Affiliations
  • Yale University (US)
  • Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut
  • Beth Israel Deaconess Medical Center (US)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2004-04-01
Volume
53
Issue
4
Pages
1060-1067
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.53.4.1060
OpenAlex
W2097447032
Cited by
534
References
59
Citations by year
2026: 6 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 26 · 2021: 20 · 2020: 19 · 2019: 18 · 2018: 20 · 2017: 23 · 2016: 19 · 2015: 37 · 2014: 27 · 2013: 27 · 2012: 22
FWCI
25.25
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
American Diabetes Association
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
interleukin-6, IL-10, insulin resistance, hepatic glucose production, PI3K signaling, insulin receptor substrate 2, IRS-1, fatty acyl-CoA, inflammatory cytokines, hyperinsulinemic-euglycemic clamp, type 2 diabetes
MeSH terms
Animals, Blood Glucose, Hyperinsulinism, Infusions, Intravenous, Insulin, Lipids, Liver, Male, Mice, Inbred C57BL, Glucose Clamp Technique, Signal Transduction, Interleukin-6, Interleukin-10, Muscle, Skeletal, 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 ›

Are you an author, or do you see a problem with this page? Request a review