A potent, non-toxic insulin-releasing peptide isolated from an extract of the skin of the Asian frog, Hylarana guntheri (Anura:Ranidae)

J. Michael Conlon, Gavin J. Power, Yasser H.A. Abdel-Wahab, Peter R. Flatt, Hu Jiansheng, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert Vaudry

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Peptides in extract of the skin of the Asian frog Hylarana guntheri Boulenger,1882 were purified by reversed-phase HPLC and individual components analysed for their ability to release insulin from the rat BRIN-BD11 clonal β cell line. The most potent peptide identified in the extract belonged to the brevinin-2 family (brevinin-2GUb; GVIIDTLKGAAKTVAAELLRKAHCKLTNSC). Other peptides with weaker insulin-releasing activity belonged to the brevinin-1 (2 peptides), brevinin-2 (2 peptides) and temporin (3 peptides) families. Only the brevinin-1 peptides showed cytolytic activity against the BRIN-BD11 cells, as demonstrated by an increased rate of release of the cytosolic enzyme, lactate dehydrogenase. A synthetic replicate of brevinin-2GUb produced a significant stimulation of insulin release (139% of basal rate; P < 0.05) at a concentration of 100 nM with a maximum response of 373% of basal rate at a concentration of 3 μM) by a mechanism that did not involve mobilization of intracellular calcium. Brevinin-2GUb also inhibited the growth of microorganisms (MIC against Escherichia coli = 32 μM, Staphylococcus aureus = 64 μM, and Candida albicans = 64 μM) but had only weak hemolytic activity against human erythrocytes (LC50 = 700 μM). Administration of brevinin-2GUb (75 nmol/kg body weight) into mice significantly (P < 0.05) improved glucose tolerance following a intraperitoneal injection of glucose, thereby demonstrating that the peptide shows potential for development into a therapeutically valuable agent for the treatment of Type 2 diabetes.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalRegulatory Peptides
Volume151
Issue number1-3
DOIs
Publication statusPublished - Nov 29 2008
Externally publishedYes

Keywords

  • Antimicrobial
  • Brevinin-2
  • Frog skin
  • Insulin secretion
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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