Reduction of disulfides by thioredoxin. Exceptional reactivity of insulin and suggested functions of thioredoxin in mechanism of hormone action.

with insulin disulfides was estimated from fluorescence measurements and the enzymatic rates to be around 1 X 10’ M-’ s-l. This is around 10,000 times higher than the second order rate constant for the reaction between insulin and dithiothreitol, demonstrating the high affinity of insulin for thioredoxin-(SH)z. Nondisulfide oxidants such as Cu2+ ions, diamide, and vitamin KI, which are known to mimic the effects of insulin on cellular hexose transport, were rapidly reduced by the thioredoxin system. The exceptional reactivity of insulin and thioredoxin-(SH)2, in vitro, is consistent with a physiological function for mammalian thioredoxin in the degradation of insulin. Functions for thioredoxin in the “thiol oxidation-reduction model” of insulin action are discussed.