TNF-alpha stimulates glucose uptake in L6 myoblasts

Diabetes Res Clin Pract. 1996 Apr;32(1-2):11-8. doi: 10.1016/0168-8227(96)01221-1.


The mechanism of TNF-alpha to regulate glucose metabolism remains unclear. To further delineate the TNF-alpha signal transduction pathway mediating glucose metabolism, we utilized L6 rat myoblasts which contain the receptors for the insulin-like growth factor-I (IGF-I) and TNF-alpha, and the ability of both ligands to stimulate glucose uptake was compared. IGF-I (6.5 nM) maximally stimulated glucose uptake 7-fold after 24 h incubation, while 23 nM TNF-alpha maximally stimulated glucose uptake 3-fold only after 48 h incubation. IGF-I receptor beta-subunit, insulin receptor substrate-1 (IRS-1), and mitogen-activated protein (MAP) kinase were all phosphorylated in response to 6.5 nM IGF-I after 10 min incubation. In contrast, the treatment with 23 nM TNF-alpha failed to phosphorylate either IGF-I receptor beta-subunit or IRS-1 but did phosphorylate MAP kinase as much as IGF-I did. Despite a similar extent to which TNF-alpha induced MAP kinase phosphorylation as IGF-I did, TNF-alpha stimulated glucose uptake less compared to IGF-I. The results indicate that MAP kinase phosphorylation is not sufficient for glucose uptake in L6 myoblasts. TNF-alpha-elicited signal transduction to glucose uptake may utilize a different pathway from that seen with IGF-I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Line
  • Deoxyglucose / metabolism*
  • Glucose / metabolism*
  • Insulin / pharmacology
  • Insulin Receptor Substrate Proteins
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Kinetics
  • Muscle Fibers, Skeletal
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Radioligand Assay
  • Rats
  • Receptor, IGF Type 1 / drug effects
  • Receptor, IGF Type 1 / physiology*
  • Receptors, Tumor Necrosis Factor / drug effects
  • Receptors, Tumor Necrosis Factor / physiology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Phosphoproteins
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Insulin-Like Growth Factor I
  • Deoxyglucose
  • Receptor, IGF Type 1
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glucose