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Bacitracin an inhibitor of the insulin degrading activity of glutathione insulin transhydrogenase

, : Bacitracin an inhibitor of the insulin degrading activity of glutathione insulin transhydrogenase. Biochemical & Biophysical Research Communications 98(2): 431-438

The antibiotic bacitracin, a known inhibitor of insulin degradation by both isolated cells and subcellular organelles, inhibited the ability of purified glutathione-insulin transhydrogenase to split insulin into its constituent A and B chains. This inhibition was demonstated by measuring the formation of insulin degradative products that were both soluble in 5% trichloroacetic acid and chromatographed as the separate chains of insulin on Sephadex G-50. At concentrations of 90 and 300 .mu.M, bacitracin inhibited 50 and 90%, respectively, of the degrading activity of the purified enzyme. Similarly, degradation by crude rat liver lysates was inhibited 50 and 90% by 70 and 250 .mu.M bacitracin, respectively. Kinetic studies indicated that this inhibition was by a complex mechanism that decreased both the Vmax and affinity of the enzyme for insulin. These data raise the possibility that the inhibition of glutathione-insulin transhydrogenase by bacitracin could account for part or all of the effects of this antibiotic on inhibition of insulin degradation by target cells.


PMID: 7013763

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