A peptide of the phylloseptin family from the skin of the frog Hylomantis lemur (Phyllomedusinae) with potent in vitro and in vivo insulin-releasing activity

Yasser Abdel-Wahab, Gavin J. Power, Peter Flatt, Douglas C. Woodhams, Louise A. Rollins-Smith, J. Michael Conlon

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

A peptide with the ability to release insulin from the rat BRIN-BD11 clonal beta cell line was isolated from norepinephrine-stimulated skin secretions of the Lemur leaf frog Hylomantis lemur Boulenger, 1882. Determination of the primary structure (FLSLIPHVISALSSL.NH2) demonstrated that the peptide belongs to the phylloseptin family whose members have previously been identified in other Phyllomedusinae species. A synthetic replicate of the peptide, termed phylloseptin-L2, produced a significant stimulation of insulin release (134% of basal rate, P <0.01) from BRIN-BD11 cells at a concentration of 30 nM, with a maximum response (301% of basal rate, P <0.001) at a concentration of 3 mu M. Phylloseptin-L2 did not stimulate release of the cytosolic enzyme, lactate dehydrogenase at concentrations up to 3 mu M, indicating that the integrity of the plasma membrane had been preserved. The stimulatory action was maintained in the absence of extracellular Ca2+ and in the presence of veraparmil (50 microM) and diazoxide (300 microM) suggesting that mechanism of action of the peptide did not primarily involve influx of Ca2+ or closure of ATP-sensitive K+ channels. Administration of phylloseptin-L2 (50 nmol/kg body weight) into mice significantly (P <0.05) increased total release of insulin and improved glucose tolerance during the 60 min period following an intraperitoneal injection of glucose (18 mmol/kg body weight). It is concluded that the peptide shows potential for development into a therapeutically valuable agent for the treatment of Type 2 diabetes. (c) 2008 Elsevier Inc. All rights reserved.
LanguageEnglish
Pages2136-2143
JournalPeptides
Volume29
Issue number12
DOIs
Publication statusPublished - Dec 2008

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Lemur
Anura
Insulin
Skin
Peptides
Body Weight
Diazoxide
Glucose
Aptitude
Intraperitoneal Injections
L-Lactate Dehydrogenase
Type 2 Diabetes Mellitus
Norepinephrine
Adenosine Triphosphate
Cell Membrane
In Vitro Techniques
Cell Line
Enzymes

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title = "A peptide of the phylloseptin family from the skin of the frog Hylomantis lemur (Phyllomedusinae) with potent in vitro and in vivo insulin-releasing activity",
abstract = "A peptide with the ability to release insulin from the rat BRIN-BD11 clonal beta cell line was isolated from norepinephrine-stimulated skin secretions of the Lemur leaf frog Hylomantis lemur Boulenger, 1882. Determination of the primary structure (FLSLIPHVISALSSL.NH2) demonstrated that the peptide belongs to the phylloseptin family whose members have previously been identified in other Phyllomedusinae species. A synthetic replicate of the peptide, termed phylloseptin-L2, produced a significant stimulation of insulin release (134{\%} of basal rate, P <0.01) from BRIN-BD11 cells at a concentration of 30 nM, with a maximum response (301{\%} of basal rate, P <0.001) at a concentration of 3 mu M. Phylloseptin-L2 did not stimulate release of the cytosolic enzyme, lactate dehydrogenase at concentrations up to 3 mu M, indicating that the integrity of the plasma membrane had been preserved. The stimulatory action was maintained in the absence of extracellular Ca2+ and in the presence of veraparmil (50 microM) and diazoxide (300 microM) suggesting that mechanism of action of the peptide did not primarily involve influx of Ca2+ or closure of ATP-sensitive K+ channels. Administration of phylloseptin-L2 (50 nmol/kg body weight) into mice significantly (P <0.05) increased total release of insulin and improved glucose tolerance during the 60 min period following an intraperitoneal injection of glucose (18 mmol/kg body weight). It is concluded that the peptide shows potential for development into a therapeutically valuable agent for the treatment of Type 2 diabetes. (c) 2008 Elsevier Inc. All rights reserved.",
author = "Yasser Abdel-Wahab and Power, {Gavin J.} and Peter Flatt and Woodhams, {Douglas C.} and Rollins-Smith, {Louise A.} and Conlon, {J. Michael}",
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language = "English",
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pages = "2136--2143",
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A peptide of the phylloseptin family from the skin of the frog Hylomantis lemur (Phyllomedusinae) with potent in vitro and in vivo insulin-releasing activity. / Abdel-Wahab, Yasser; Power, Gavin J.; Flatt, Peter; Woodhams, Douglas C.; Rollins-Smith, Louise A.; Conlon, J. Michael.

Vol. 29, No. 12, 12.2008, p. 2136-2143.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A peptide of the phylloseptin family from the skin of the frog Hylomantis lemur (Phyllomedusinae) with potent in vitro and in vivo insulin-releasing activity

AU - Abdel-Wahab, Yasser

AU - Power, Gavin J.

AU - Flatt, Peter

AU - Woodhams, Douglas C.

AU - Rollins-Smith, Louise A.

AU - Conlon, J. Michael

PY - 2008/12

Y1 - 2008/12

N2 - A peptide with the ability to release insulin from the rat BRIN-BD11 clonal beta cell line was isolated from norepinephrine-stimulated skin secretions of the Lemur leaf frog Hylomantis lemur Boulenger, 1882. Determination of the primary structure (FLSLIPHVISALSSL.NH2) demonstrated that the peptide belongs to the phylloseptin family whose members have previously been identified in other Phyllomedusinae species. A synthetic replicate of the peptide, termed phylloseptin-L2, produced a significant stimulation of insulin release (134% of basal rate, P <0.01) from BRIN-BD11 cells at a concentration of 30 nM, with a maximum response (301% of basal rate, P <0.001) at a concentration of 3 mu M. Phylloseptin-L2 did not stimulate release of the cytosolic enzyme, lactate dehydrogenase at concentrations up to 3 mu M, indicating that the integrity of the plasma membrane had been preserved. The stimulatory action was maintained in the absence of extracellular Ca2+ and in the presence of veraparmil (50 microM) and diazoxide (300 microM) suggesting that mechanism of action of the peptide did not primarily involve influx of Ca2+ or closure of ATP-sensitive K+ channels. Administration of phylloseptin-L2 (50 nmol/kg body weight) into mice significantly (P <0.05) increased total release of insulin and improved glucose tolerance during the 60 min period following an intraperitoneal injection of glucose (18 mmol/kg body weight). It is concluded that the peptide shows potential for development into a therapeutically valuable agent for the treatment of Type 2 diabetes. (c) 2008 Elsevier Inc. All rights reserved.

AB - A peptide with the ability to release insulin from the rat BRIN-BD11 clonal beta cell line was isolated from norepinephrine-stimulated skin secretions of the Lemur leaf frog Hylomantis lemur Boulenger, 1882. Determination of the primary structure (FLSLIPHVISALSSL.NH2) demonstrated that the peptide belongs to the phylloseptin family whose members have previously been identified in other Phyllomedusinae species. A synthetic replicate of the peptide, termed phylloseptin-L2, produced a significant stimulation of insulin release (134% of basal rate, P <0.01) from BRIN-BD11 cells at a concentration of 30 nM, with a maximum response (301% of basal rate, P <0.001) at a concentration of 3 mu M. Phylloseptin-L2 did not stimulate release of the cytosolic enzyme, lactate dehydrogenase at concentrations up to 3 mu M, indicating that the integrity of the plasma membrane had been preserved. The stimulatory action was maintained in the absence of extracellular Ca2+ and in the presence of veraparmil (50 microM) and diazoxide (300 microM) suggesting that mechanism of action of the peptide did not primarily involve influx of Ca2+ or closure of ATP-sensitive K+ channels. Administration of phylloseptin-L2 (50 nmol/kg body weight) into mice significantly (P <0.05) increased total release of insulin and improved glucose tolerance during the 60 min period following an intraperitoneal injection of glucose (18 mmol/kg body weight). It is concluded that the peptide shows potential for development into a therapeutically valuable agent for the treatment of Type 2 diabetes. (c) 2008 Elsevier Inc. All rights reserved.

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DO - 10.1016/j.peptides.2008.09.006

M3 - Article

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SP - 2136

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ER -