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Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

Bouzakri, K. and Plomgaard, P. and Berney, T. and Donath, M. Y. and Pedersen, B. K. and Halban, P. A.. (2011) Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle. Diabetes, Vol. 60, H. 4. pp. 1111-1121.

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Official URL: http://edoc.unibas.ch/dok/A6005449

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Abstract

OBJECTIVE: Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) beta-cells. RESEARCH DESIGN AND METHODS: Human skeletal muscle cells were cultured for up to 24 h with tumor necrosis factor (TNF)-alpha to induce insulin resistance, and mRNA expression for cytokines was analyzed and compared with controls (without TNF-alpha). Conditioned media were collected and candidate cytokines were measured by antibody array. Human and rat primary beta-cells were used to explore the impact of exposure to conditioned media for 24 h on apoptosis, proliferation, short-term insulin secretion, and key signaling protein phosphorylation and expression. RESULTS: Human myotubes express and release a different panel of myokines depending on their insulin sensitivity, with each panel exerting differential effects on beta-cells. Conditioned medium from control myotubes increased proliferation and glucose-stimulated insulin secretion (GSIS) from primary beta-cells, whereas conditioned medium from TNF-alpha-treated insulin-resistant myotubes (TMs) exerted detrimental effects that were either independent (increased apoptosis and decreased proliferation) or dependent on the presence of TNF-alpha in TM (blunted GSIS). Knockdown of beta-cell mitogen-activated protein 4 kinase 4 prevented these effects. Glucagon-like peptide 1 protected beta-cells against decreased proliferation and apoptosis evoked by TMs, while interleukin-1 receptor antagonist only prevented the latter. CONCLUSIONS: Taken together, these data suggest a possible new route of communication between skeletal muscle and beta-cells that is modulated by insulin resistance and could contribute to normal beta-cell functional mass in healthy subjects, as well as the decrease seen in type 2 diabetes.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Infection Biology (Khanna)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Diabetes Research (Donath)
UniBasel Contributors:Donath, Marc
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Diabetes Association
ISSN:0012-1797
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:13
Deposited On:25 Oct 2013 08:32

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