Insulin-releasing properties of the frog skin peptide pseudin-2 and its [Lys18]-substituted analogue

Yasser H.A. Abdel-Wahab, Gavin J. Power, Ming T. Ng, Peter R. Flatt, J. Michael Conlon

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34 Citations (Scopus)

Abstract

Pseudin-2 is a cationic α-helical peptide that was first isolated from the skin of the paradoxical frog Pseudis paradoxa on the basis of its antimicrobial activity. We have investigated the insulin-releasing properties and cytotoxicity of the peptide, together with selected analogues with increased cationicity and hydrophobicity. At concentrations in the range 10 -9-10-6 m, pseudin-2, and its [Lys18], [Phe8], and [d-Lys3,d-Lys10,d-Lys14] derivatives, stimulated insulin release from the BRIN-BD11 clonal β-cell line without increasing release of lactate dehydrogenase. The [Lys18] analogue was the most potent (46% increase in insulin release at 10 -9 m) and the most effective (215% increase in insulin release at 10-6 m). The more cationic [Lys3,Lys10,Lys 14] and [Lys3,Lys10,Lys14,Lys 21] analogues lacked insulinotropic action and the more hydrophobic [Phe16] analogue was cytotoxic at concentrations ≥10-7 m. Pseudin-2 and [Lys18]-pseudin-2 had no effect on intracellular calcium concentrations and stimulated insulin release in the absence of external calcium. [Lys18]-pseudin-2 (10-8 m) stimulated insulin release in the presence of diazoxide and verapamil. Our results demonstrate that pseudin-2 stimulates insulin secretion from BRIN-BD11 cells by a mechanism involving Ca2+-independent pathways and identify [Lys 18]-pseudin-2 as a peptide that may have potential for development as a therapeutically valuable insulinotropic agent for the treatment of type 2 diabetes.

Original languageEnglish
Pages (from-to)143-148
Number of pages6
JournalBiological Chemistry
Volume389
Issue number2
DOIs
Publication statusPublished - Feb 1 2008
Externally publishedYes

Keywords

  • Frog skin
  • Insulin secretion
  • Pseudin-2
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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