Cited by 65Adipokines, Inflammation, and Metabolic DiseasesCytokine Signaling Pathways and InteractionsMetabolism, Diabetes, and Cancer

Altered Response of Skeletal Muscle to IL-6 in Type 2 Diabetic Patients

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Jiang, Lake Q., Duque-Guimaraes, Daniella E., Machado, Ubiratan F., Zierath, Juleen R., Krook, Anna·2013·Diabetes

Abstract

Interleukin-6 (IL-6) has a dual role in modulating insulin sensitivity, with evidence for this cytokine as both an enhancer and inhibitor of insulin action. We determined the effect of IL-6 exposure on glucose and lipid metabolism in cultured myotubes established from people with normal glucose tolerance or type 2 diabetes. Acute IL-6 exposure increased glycogen synthesis, glucose uptake, and signal transducer and activator of transcription 3 (STAT3) phosphorylation in cultured myotubes from normal glucose tolerant subjects. However, in type 2 diabetic patients, IL-6 was without effect on glucose metabolism and STAT3 signaling, concomitant with increased suppressor of cytokine signaling 3 (SOCS3) expression. IL-6 increased fatty acid oxidation in myotubes from type 2 diabetic and normal glucose tolerant subjects. Expression of IL-6, IL-6 receptor (IL-6R), or glycoprotein 130, as well as IL-6 secretion, was unaltered between cultured myotubes from normal glucose tolerant or type 2 diabetic subjects. Circulating serum IL-6 concentration was unaltered between normal glucose tolerant and type 2 diabetic subjects. In summary, skeletal muscle cells from type 2 diabetic patients display selective IL-6 resistance for glucose rather than lipid metabolism. In conclusion, IL-6 appears to play a differential role in regulating metabolism in type 2 diabetic patients compared with normal glucose tolerant subjects.

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  • Effects of IL-6 on glucose metabolism are largely attributed to exercise-mediated activation of AMPK, an effect not observed for IL-6 released in context of T2DM.

    “The effects of IL-6 on glucose metabolism are largely attributed to the exercise-mediated activation of AMPK, an effect that is not observed for IL-6 released in the context of T2DM [47].”

    From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [47]

    The Results (IL-6 activation of intracellular signaling pathways; page unavailable) report that IL-6 increased AMPK phosphorylation to a similar extent in myotubes from subjects with normal glucose tolerance and type 2 diabetes. The Discussion likewise says this AMPK response was preserved in type 2 diabetes. Although IL-6’s effects on glucose uptake and glycogen synthesis were impaired, the claimed absence of AMPK activation is contrary to the paper. (LLM, conf=0.90)

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Authors
Jiang, L. Q., Duque-Guimaraes, D. E., Machado, U. F., Zierath, J. R., & Krook, A.
Affiliations
  • Karolinska Institutet (SE)
  • Universidade de São Paulo (BR)
Corresponding author
Krook, Anna
Venue
Diabetes
Published
2013-01-17
Volume
62
Issue
2
Pages
355-361
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2118235554
Cited by
65
References
45
Citations by year
2026: 2 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 8 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 11 · 2013: 6
FWCI
5.01
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Petrus och Augusta Hedlunds Stiftelse
  • Fundação de Amparo à Pesquisa do Estado de São Paulo
  • Karolinska Institutet
  • Novo Nordisk
  • Vetenskapsrådet
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
interleukin-6, type 2 diabetes, skeletal muscle, myotubes, insulin resistance, glucose metabolism, lipid metabolism, STAT3 signaling, SOCS3, glycogen synthesis, glucose uptake, fatty acid oxidation, IL-6 receptor, gp130, cytokine resistance
MeSH terms
Suppressor of Cytokine Signaling 3 Protein, Animals, Cells, Cultured, Diabetes Mellitus, Type 2, Fatty Acids, Female, Glucose, Glycogen, Glycoproteins, Humans, Insulin Resistance, Male, Mice, Inbred C57BL, Middle Aged, Phosphorylation, Interleukin-6, Muscle, Skeletal, Muscle Fibers, Skeletal, Receptors, Interleukin-6, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice

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