Structure-function studies on enterostatin inhibition of insulin release
Year: 2019
Type: article
Abstract: The pentapeptide enterostatin (Val-Pro-Asp-Pro-Arg or VPDPR1) has been shown to inhibit insulin secretion both in vivo and in isolated rat islets. We report on structure-function studies of enterostatin in rat islets and in RINm5F insulinoma cells. In isolated rat islets, the tyrosinated version of enterostatin (YVPDPR) had ~10 fold reduced potency at lower concentrations (10nM versus 1nM) in inhibiting insulin release compared to nascent enterostatin and did not exhibit activity at 1μM concentrations. Replacement of the L-valine with D-valine caused total loss of biological activity. The peptide YPDPR was more efficacious than native enterostatin at 0.1nM but lost activity at higher concentrations. However, in RINm5F cells, the inhibitory effect of YPDPR was preserved. 3-iodo- YPDPR exhibited a similar inhibitory profile to enterostatin across a wide concentration. These studies demonstrate the functional importance of the N-terminal sequences of enterostatin in regulating insulin secretion but also suggest tolerance to some modifications. Radio-iodinated-YPDPR may be useful in characterising putative enterostatin receptors.
DOI: 10.1159/000497547
Authors: M. Tadayyon, S. Liou, C.P. Briscoe, G. Badman, D.S. Eggleston, J.R.S. Arch, D.A. York
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4401912582