Suppressor of Cytokine Signaling 3 Expression and Insulin Resistance in Skeletal Muscle of Obese and Type 2 Diabetic Patients
Abstract
Interleukin-6 (IL-6) could be a possible mediator of insulin resistance. We investigated whether IL-6 could inhibit insulin signaling in human skeletal myotubes and whether suppressor of cytokine signaling 3 (SOCS-3) could be related to insulin resistance in vivo in humans. IL-6 inhibited insulin signaling and induced SOCS-3 expression in differentiated myotubes. SOCS-3 mRNA levels were significantly increased in the skeletal muscle of type 2 diabetic patients compared with control subjects and correlated with reduced insulin-stimulated glucose uptake. In contrast, SOCS-3 mRNA levels were reduced in muscle of obese nondiabetic subjects compared with type 2 diabetic patients, despite similar circulating concentrations of IL-6. Increased SOCS-3 mRNA levels in diabetes were not attributable to hyperglycemia, as type 1 diabetic patients had normal SOCS-3 mRNA expression in muscle. However, the combination of high glucose and IL-6 levels in type 2 diabetic patients may induce SOCS-3 expression, as has been seen in human muscle cells. In subcutaneous adipose tissue, SOCS-3 mRNA levels were increased in obese individuals and strongly correlated with IL-6 expression, supporting a paracrine effect of IL-6 on SOCS-3 expression in fat. Taken together, our results showed that SOCS-3 expression in human skeletal muscle in vivo is not related to insulin resistance in the presence of elevated IL-6 concentrations and suggest that cytokine action could differ in type 2 diabetic patients and nondiabetic obese subjects.
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Human skeletal muscle cells in culture are known to respond to interleukin-6.
“In separate studies, we selected human skeletal muscle cells in culture that are known to respond to interleukin-6 (39).”
From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [39]
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 [39]
Interleukin-6 interferes with insulin signaling in muscle and hepatic cells.
“Several reports indicate that interleukin-6 interferes with insulin signaling in muscle and hepatic cells (39,55)”
From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [39]
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References 53 · Cited by 200
- Authors
- Rieusset, J., Bouzakri, K., Chevillotte, E., Ricard, N., Jacquet, D., Bastard, J.-P., Laville, M., & Vidal, H.
- Affiliations
- Lyon 1 Université (FR)
- INSERM U449/INRA U1235 and Centre de Recherche en Nutrition Humaine de Lyon, IFR 62, Faculté de Médecine René Laennec, Université Claude Bernard Lyon-1, Lyon, France
- Inserm (FR)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-09-01
- Volume
- 53
- Issue
- 9
- Pages
- 2232-2241
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2137976281
- Cited by
- 200
- References
- 53
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 10 · 2016: 8 · 2015: 7 · 2014: 10 · 2013: 13 · 2012: 14
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Institut National de la Recherche Agronomique
- Institut de Recherches Servier
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- SOCS3, insulin resistance, interleukin-6, skeletal muscle, type 2 diabetes, obesity, insulin signaling, insulin-stimulated glucose uptake, subcutaneous adipose tissue, cytokine signaling, type 1 diabetes
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Adipose Tissue, Adult, Cells, Cultured, Diabetes Mellitus, Diabetes Mellitus, Type 2, Female, Humans, Hyperglycemia, Insulin, Insulin Resistance, Male, Middle Aged, Obesity, Repressor Proteins, RNA, Messenger, Transcription Factors, Signal Transduction, Interleukin-6, Gene Expression, Muscle, Skeletal, Muscle Fibers, Skeletal, Suppressor of Cytokine Signaling Proteins
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