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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

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Abdel-Wahab, Yasser, Power, Gavin J., Flatt, Peter, Woodhams, Douglas C., Rollins-Smith, Louise A. and Conlon, J. Michael (2008) 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. PEPTIDES, 29 (12). pp. 2136-2143. [Journal article]

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DOI: 10.1016/j.peptides.2008.09.006

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.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2909
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 09:41
Last Modified:11 Feb 2010 14:24

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