Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.56 (insulin-degrading enzyme)
 737 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to determine whether transepithelial transport of insulin can be improved by enzyme inhibitors and whether insulin concentration affects its ileal absorption. Ussing chambers and radioimmunoassay were used to study insulin transport across the rat ileum, and circular dichroic spectra were used to determine whether insulin aggregated at high concentrations. Inhibitors that inhibit insulin-degrading enzyme, including N-ethylmaleimide, 1,10-phenanthroline and p-chloromercuribenzoate, dramatically improved insulin transport across the ileum. At 100 nm, the ileal permeability of immunoreactive insulin was 10(-6) cm s-1 in the presence of inhibitors, and was negligible when inhibitors were not used. Ammonium chloride, a lysosomotropic agent that increases intralysosomal pH, and aprotinin, a proteasome inhibitor, did not increase transport of insulin to a detectable extent. Insulin permeability decreased as its concentration increased from 100 nm to 83.3 microM, and at 83.3 microM insulin aggregated. It is concluded that insulin transport is improved by enzyme inhibitors, but is impaired by insulin aggregation at high concentrations.
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PMID:Effects of enzyme inhibitors and insulin concentration on transepithelial transport of insulin in rats. 895 12