TNF-ALPHA STIMULATES GLUCOSE-UPTAKE IN L6 MYOBLASTS

The mechanism of TNF-alpha to regulate glucose metabolism remains uncl ear. To further delineate the TNF-alpha signal transduction pathway me diating glucose metabolism, we utilized L6 rat myoblasts which contain the receptors for the insulin-like growth factor-I (IGF-I) and TNF-al pha, and the ability of both ligands to stimulate glucose uptake was c ompared. IGF-I (6.5 nM) maximally stimulated glucose uptake 7-fold aft er 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 fa iled to phosphorylate either IGF-I receptor beta-subunit or IRS-I but did phosphorylate MAP kinase as much as IGF-I did. Despite a similar e xtent to which TNF-alpha induced MAP kinase phosphorylation as IGF-I d id, TNF-alpha stimulated glucose uptake less compared to IGF-I. The re sults indicate that MAP kinase phosphorylation is not sufficient for g lucose uptake in L6 myoblasts. TNF-alpha-elicited signal transduction to glucose uptake may utilize a different pathway from that seen with IGF-I.