TNF inhibits insulin induced STAT5 activation in differentiated mouse muscle cells pmi28

Tumor necrosis factor (TNF) plays a central role in the state of insulin re sistance leading to type II diabetes. We here describe the crosstalk of TNF with insulin signaling cascades in the mouse muscle cell line pmi28. TNF d ownregulated insulin induced insulin receptor kinase activity and insulin i nduced activation of the transcription factor STAT5. Our results provide ev idence that the inhibitory crosstalk between TNF and insulin in skeletal mu scle cells comprises an interference with the expression of STAT5 regulated genes which may play an important role in the manifestation and/or progres sion of insulin resistance in muscle cells. (C) 1998 Federation of European Biochemical Societies.