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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 389, Issue 2


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
  • 5Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, 17666 Al-Ain, United Arab Emirates
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Published Online: 2008-01-28 | DOI: https://doi.org/10.1515/BC.2008.018


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,Lys14] and [Lys3,Lys10,Lys14,Lys21] 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 [Lys18]-pseudin-2 as a peptide that may have potential for development as a therapeutically valuable insulinotropic agent for the treatment of type 2 diabetes.

Keywords: frog skin; insulin secretion; pseudin-2; type 2 diabetes

About the article

Corresponding author

Received: 2007-09-13

Accepted: 2007-10-30

Published Online: 2008-01-28

Published in Print: 2008-02-01

Citation Information: Biological Chemistry, Volume 389, Issue 2, Pages 143–148, ISSN (Online) 14374315, ISSN (Print) 14316730, DOI: https://doi.org/10.1515/BC.2008.018.

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