The proinflammatory cytokine tumor necrosis factor-α increases the amount of glucose transporter-4 at the surface of muscle cells independently of changes in interleukin-6

Nerea Roher, Victor Samokhvalov, Mònica Díaz, Simon MacKenzie, Amira Klip, Josep V. Planas

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

TNFα is a proinflammatory cytokine secreted by macrophages in response to bacterial infection. Recently new evidence has emerged suggesting that stressed or injured myocytes produce TNFα that then acts as an autocrine and/or paracrine mediator. TNFα receptors types 1 and 2 are present in skeletal muscle cells, and muscle cells can secrete, in addition to TNFα, other cytokines such as IL-1β or IL-6. Furthermore, the plasma concentration of TNFα is elevated in insulin-resistant states associated with obesity and type 2 diabetes. Here we show that TNFα increased the amount of glucose transporter (GLUT)-4 at the plasma membrane and also glucose uptake in the L6 muscle cell line stably expressing GLUT4 tagged with the c-myc epitope. Regardless of the state of differentiation of the L6 cells, TNFα did not affect the rate of proliferation or of apoptosis. The stimulatory effects of TNFα on cell surface GLUT4 and glucose uptake were blocked by nuclear factor-κB and p38MAPK pathway specific inhibitors (Bay 11-7082 and SB220025), and these two pathways were stimulated by TNFα. Furthermore, although TNFα increased IL-6 mRNA and protein expression, IL-6 did not mediate the effects of TNFα on cell surface GLUT4 levels, which also did not require de novo protein synthesis. The results indicate that TNFα can stimulate glucose uptake in L6 muscle cells by inducing GLUT4 translocation to the plasma membrane, possibly through activation of the nuclear factor-κB and p38MAPK signaling pathways and independently of the production of IL-6. Copyright © 2008 by The Endocrine Society.
Original languageEnglish
Pages (from-to)1880-1889
JournalEndocrinology
Volume149
DOIs
Publication statusPublished - 1 Apr 2008

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