Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone

Biochem Biophys Res Commun. 2003 Nov 14;311(2):372-9. doi: 10.1016/j.bbrc.2003.10.013.


IL-6 has emerged as an important cytokine upregulated in states of insulin resistance such as type 2 diabetes. We evaluated the chronic effect of IL-6 on insulin signaling in 3T3-F442A and 3T3-L1 adipocytes. First, cells responded to a chronic treatment with IL-6 by initiating an autoactivation process that increased IL-6 secretion. Second, IL-6-treated adipocytes showed a decreased protein expression of IR-beta subunit and IRS-1 but also an inhibition of the insulin-induced activation of IR-beta, Akt/PKB, and ERK1/2. Moreover, IL-6 suppressed the insulin-induced lipogenesis and glucose transport consistent with a diminished expression of GLUT4. IL-6-treated adipocytes failed to maintain their adipocyte phenotype as shown by the downregulation of the adipogenic markers FAS, GAPDH, aP2, PPAR-gamma, and C/EBP-alpha. IL-6 also induced the expression of SOCS-3, a potential inhibitor of insulin signaling. Finally, the effects of IL-6 could be prevented by rosiglitazone, an insulin-sensitizing agent. Thus, IL-6 may play an important role in the set-up of insulin resistance in adipose cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism*
  • Animals
  • Dose-Response Relationship, Drug
  • Glucose / metabolism*
  • Insulin Resistance / physiology*
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology*
  • Mice
  • Proteins / metabolism*
  • Repressor Proteins*
  • Rosiglitazone
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Thiazolidinediones / pharmacology*
  • Transcription Factors*
  • Up-Regulation / drug effects*
  • Up-Regulation / physiology


  • Interleukin-6
  • Proteins
  • Repressor Proteins
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Thiazolidinediones
  • Transcription Factors
  • Rosiglitazone
  • Glucose