title: TNF-alpha stimulates glucose uptake in L6 myoblasts.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Takino
authors.forename: H
authors.initials: H
authors.lastname: Matsuo
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Uotani
authors.forename: S
authors.initials: S
authors.lastname: Akazawa
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Nagataki
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D003847:Deoxyglucose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D018485:Muscle Fibers, Skeletal; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011869:Radioligand Assay; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D017526:Receptor, IGF Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005947:Glucose