The effect of inhibitors of insulin processing on generation of insulin intermediate products from human fibroblast as detected by high performance liquid chromatography (HPLC)
Kitabchi, A.E.; Stentz, F.B.
Biochemical and Biophysical Research Communications 128(1): 163-170
1985
ISSN/ISBN: 0006-291X PMID: 3885945 Document Number: 263098
To assess the role of various modulators of insulin processing on cell-associated A14-125I-insulin intermediates in human fibroblasts, the effects of N-ethylmaleimide (NEM), chloroquine, bacitracin, dansylcadavarin and phenylarsine oxide on generation of these intermediate products were studied with the use of HPLC . NEM completely inhibited generation of intermediate peaks or iodotyrosine. Chloroquine inhibited conversion of A14-125I-insulin to iodotyrosine by about 75% and the remaining A14-125I-insulin was not susceptible to acid wash. Bacitracin, dansylcadaverine and phenylarsine oxide stimulated formation of intermediate products with concomitant inhibition of iodotyrosine formation. There are at least 3 components of insulin degradation in human fibroblasts. These include the sulfhydryl group inhibitor-sensitive, the intracellular chloroquine-sensitize, and membrane site inhibitor-sensitive components.