Tumor necrosis factor alpha (TNFalpha) was found to be significantly increased in skeletal muscles and retroperitoneal fat of obese insulin-resistant Koletsky rats as compared to control Wistar rats. This increase was accompanied by a depression of insulin receptor protein tyrosine kinase (PTK) activity. Neither the insulin-binding capacity nor insulin receptor affinity were related to this TNFalpha increase in these tissues. In the liver, no significant changes of TNFalpha content and only a lowering of insulin-binding capacity were found. It is concluded that an increased TNFalpha content in muscles and fat (but not in the liver) contributes to insulin resistance by lowering insulin receptor protein tyrosine kinase activity, while other insulin receptor characteristics (insulin-binding capacity and affinity of insulin receptors to the hormone) do not seem to be influenced by this factor.

Institute of Pathological Physiology Medical Faculty Palacký University Olomouc Czech Republic