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Impairment of Insulin Signaling in Human Skeletal Muscle Cells by Co-Culture With Human Adipocytes

Open access
Dietze, Daniela, Koenen, Marlis, Röhrig, Karin, Horikoshi, Hiroyoshi, Hauner, Hans, Eckel, Jürgen·2002·Diabetes

Abstract

Adipocyte factors play a major role in the induction of insulin resistance in skeletal muscle. To analyze this cross-talk, we established a system of co-culture of human fat and skeletal muscle cells. Cells of three muscle donors were kept in co-culture with cells of various fat cell donors, and insulin signaling was subsequently analyzed in myocytes. Insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was completely blocked, with unaltered expression of IRS-1. Troglitazone increased insulin action on IRS-1 phosphorylation, in both the absence and presence of co-culture. Insulin-regulated activation of Akt kinase in the myocytes was significantly reduced after co-culture, with troglitazone restoring insulin action. Addition of tumor necrosis factor (TNF)-α (2.5 nmol/l) to myocytes for 48 h reduced IRS-1 expression and inhibited IRS-1 and Akt phosphorylation comparable to the effect of co-culture. Lower doses of TNF-α were ineffective. After co-culture, TNF-α in the culture medium was below the detection limit of 0.3 pmol/l. A very low level of resistin was detected in the supernatant of myocytes, but not of adipocytes. In conclusion, the release of fat cell factors induces insulin resistance in human skeletal muscle cells; however, TNF-α and resistin appear not to be involved in this process.

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Metadata

Authors
Dietze, D., Koenen, M., Röhrig, K., Horikoshi, H., Hauner, H., & Eckel, J.
Venue
Diabetes
Published
2002-08-01
Volume
51
Issue
8
Pages
2369-2376
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2100098822
Cited by
183
References
7
FWCI
7.84
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Impairment of Insulin Signaling in Human Skeletal Muscle Cells by Co-Culture With Human Adipocytes. https://app.cochat.ai/papers/10.2337/diabetes.51.8.2369
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Dietze, D., Koenen, M., Röhrig, K., Horikoshi, H., Hauner, H., & Eckel, J. (2002). Impairment of Insulin Signaling in Human Skeletal Muscle Cells by Co-Culture With Human Adipocytes. Diabetes. https://doi.org/10.2337/diabetes.51.8.2369

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