Designed inhibitors of insulin-degrading enzyme regulate the catabolism and activity of insulin.

ABSTRACT:

Background

Insulin is a vital peptide hormone that is a central regulator of glucose homeostasis, and impairments in insulin signaling cause diabetes mellitus. In principle, it should be possible to enhance the activity of insulin by inhibiting its catabolism, which is mediated primarily by insulin-degrading enzyme (IDE), a structurally and evolutionarily distinctive zinc-metalloprotease. Despite interest in pharmacological inhibition of IDE as an attractive anti-diabetic approach dating to the 1950s, potent and selective inhibitors of IDE have not yet emerged.

Methodology/principal findings

We used a rational design approach based on analysis of combinatorial peptide mixtures and focused compound libraries to develop novel peptide hydroxamic acid inhibitors of IDE. The resu

SUBMITTER: Leissring MA 

PROVIDER: S-EPMC2866327 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature