Alterations in the XXXX kinase activity of the insulin receptor produced by in vitro @entity3190 .

@entity353 @entity3190 @entity367 @entity3505 @entity1720 @entity669 @entity413 @entity855
The @entity669 kinase activity of the insulin receptor was examined in fat cells made insulin resistant by @entity3190 . Adipocytes previously treated for 16 h in vitro with 0.1 microM insulin were markedly insensitive to insulin as shown by the requirement of 2.3-fold higher concentration of insulin to stimulate half-maximal activation of @entity413 metabolism ( @entity413 oxidation and @entity413 conversion to lipids). A similar rightward shift in the insulin dose-response curve was also evident for an insulin action not dependent on @entity413 metabolism, i.e. the inhibition of hormone-stimulated lipolysis. The almost 60% @entity1720 occurred in conjunction with a 37% loss in insulin-binding activity, an alteration caused by a reduction in the number of insulin receptors. Studies of @entity669 kinase activity demonstrated a preferential alteration in this insulin receptor property, in addition to the receptor loss. The insulin-stimulated Vmax for the phosphorylation of the artificial substrate, @entity367 80-Tyr20, was significantly reduced by almost 40%, when the activity was expressed per insulin binding and measured in a receptor preparation purified by @entity3505 germ affinity chromatography and immunoprecipitation. An elevation in basal @entity669 kinase activity was also present, which correlated with a lower apparent Km for @entity855 (0.025 mM) in comparison to the Km of 0.070 mM for the receptors from control cells. These findings indicate the presence of two types of alterations that involve the insulin receptor and @entity3190 : one constituted by a modest @entity353 and a second by modifications in the @entity669 kinase activity of the remaining receptors. Both alterations are required to explain the magnitude of the insulin resistance that develops after 16 h of insulin treatment.
