Insulin-releasing properties of the frog skin peptide pseudin-2 and its [Lys(18)]-substituted analogue

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

Research output: Contribution to journalArticle

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Abstract

Pseudin-2 is a cationic a-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 [Lys(18)], [Phe(8)], and [D-Lys(3), D-Lys(10), D-Lys(14)] derivatives, stimulated insulin release from the BRIN-BD11 clonal beta-cell line without increasing release of lactate dehydrogenase. The [Lys(18)] 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 [Lys(3), Lys(10), Lys(14)] and [Lys(3), Lys(10), Lys(14) Lys(21)] analogues lacked insulinotropic action and the more hydrophobic [Phe(16)] analogue was cytotoxic at concentrations >= 10(-7) M. Pseudin-2 and [Lys(18)]-pseudin-2 had no effect on intracellular calcium concentrations and stimulated insulin release in the absence of external calcium. [Lys(18)]-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.
LanguageEnglish
Pages143-148
JournalBiological Chemistry
Volume389
Issue number2
DOIs
Publication statusPublished - Feb 2008

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Skin
Insulin
Peptides
Calcium
Diazoxide
Cytotoxicity
Hydrophobicity
Medical problems
Verapamil
octadeca(lysine)
L-Lactate Dehydrogenase
Cells
Derivatives

Cite this

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title = "Insulin-releasing properties of the frog skin peptide pseudin-2 and its [Lys(18)]-substituted analogue",
abstract = "Pseudin-2 is a cationic a-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 [Lys(18)], [Phe(8)], and [D-Lys(3), D-Lys(10), D-Lys(14)] derivatives, stimulated insulin release from the BRIN-BD11 clonal beta-cell line without increasing release of lactate dehydrogenase. The [Lys(18)] 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 [Lys(3), Lys(10), Lys(14)] and [Lys(3), Lys(10), Lys(14) Lys(21)] analogues lacked insulinotropic action and the more hydrophobic [Phe(16)] analogue was cytotoxic at concentrations >= 10(-7) M. Pseudin-2 and [Lys(18)]-pseudin-2 had no effect on intracellular calcium concentrations and stimulated insulin release in the absence of external calcium. [Lys(18)]-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.",
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Insulin-releasing properties of the frog skin peptide pseudin-2 and its [Lys(18)]-substituted analogue. / Abdel-Wahab, Yasser; Power, Gavin J.; Ng, Ming T.; Flatt, Peter; Conlon, J. Michael.

In: Biological Chemistry, Vol. 389, No. 2, 02.2008, p. 143-148.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Insulin-releasing properties of the frog skin peptide pseudin-2 and its [Lys(18)]-substituted analogue

AU - Abdel-Wahab, Yasser

AU - Power, Gavin J.

AU - Ng, Ming T.

AU - Flatt, Peter

AU - Conlon, J. Michael

PY - 2008/2

Y1 - 2008/2

N2 - Pseudin-2 is a cationic a-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 [Lys(18)], [Phe(8)], and [D-Lys(3), D-Lys(10), D-Lys(14)] derivatives, stimulated insulin release from the BRIN-BD11 clonal beta-cell line without increasing release of lactate dehydrogenase. The [Lys(18)] 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 [Lys(3), Lys(10), Lys(14)] and [Lys(3), Lys(10), Lys(14) Lys(21)] analogues lacked insulinotropic action and the more hydrophobic [Phe(16)] analogue was cytotoxic at concentrations >= 10(-7) M. Pseudin-2 and [Lys(18)]-pseudin-2 had no effect on intracellular calcium concentrations and stimulated insulin release in the absence of external calcium. [Lys(18)]-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.

AB - Pseudin-2 is a cationic a-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 [Lys(18)], [Phe(8)], and [D-Lys(3), D-Lys(10), D-Lys(14)] derivatives, stimulated insulin release from the BRIN-BD11 clonal beta-cell line without increasing release of lactate dehydrogenase. The [Lys(18)] 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 [Lys(3), Lys(10), Lys(14)] and [Lys(3), Lys(10), Lys(14) Lys(21)] analogues lacked insulinotropic action and the more hydrophobic [Phe(16)] analogue was cytotoxic at concentrations >= 10(-7) M. Pseudin-2 and [Lys(18)]-pseudin-2 had no effect on intracellular calcium concentrations and stimulated insulin release in the absence of external calcium. [Lys(18)]-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.

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DO - 10.1515/BC.2008.018

M3 - Article

VL - 389

SP - 143

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JO - Biological Chemistry

T2 - Biological Chemistry

JF - Biological Chemistry

SN - 1431-6730

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