Brevinin-2-related Peptide and its [D4K] analogue stimulate insulin release in vitro and improve glucose tolerance in mice fed a high fat diet

Y. H.A. Abdel-Wahab, S. Patterson, P. R. Flatt, J. M. Conlon

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

The cationic, -helical frog skin antimicrobial peptide B2RP (brevinin-2-related peptide) shows sequence similarity to antimicrobial peptides belonging to the brevinin-2 family, but lacks the C-terminal cyclic heptapeptide domain (Cys-Lys-XaaCys). Synthetic B2RP produced a significant (p<0.05) stimulation of insulin release (148% of basal rate at a concentration of 1M with a maximum response of 222% of basal rate at a concentration of 3M) from BRIN-BD11 clonal -cells without increasing the release of the cytosolic enzyme, lactate dehydrogenase. Increasing cationicity of B2RP while maintaining amphipathicity by the substitution Asp 4 Lys enhanced the insulin-releasing potency (137% of basal rate at a concentration of 0.3M; p<0.05) with no stimulation of lactate dehydrogenase release. In contrast, the L18K, and D4K, L18K analogues were toxic to the cells, and the K16A analogue, with increased amphipathicity and hydrophobicity, showed reduced potency. Administration of [D4K]B2RP (100nmol/kg body weight) to mice fed a high fat diet to induce obesity and insulin-resistance significantly (p<0.05) enhanced insulin release and improved glucose tolerance during the 60-minute period following an intraperitoneal glucose load (18mmol/kg body weight). B2RP shows potential for development into an agent for the treatment of type 2 diabetes.

Original languageEnglish
Pages (from-to)652-656
Number of pages5
JournalHormone and Metabolic Research
Volume42
Issue number9
DOIs
Publication statusPublished - 2010

Keywords

  • frog skin
  • incretin peptide
  • type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint

Dive into the research topics of 'Brevinin-2-related Peptide and its [D4K] analogue stimulate insulin release in vitro and improve glucose tolerance in mice fed a high fat diet'. Together they form a unique fingerprint.

Cite this