Skin secretions of several frog species contain host-defense peptides with multiple biological activities including in vitro and in vivo insulin-releasing actions. This study investigates the effects of tigerinin-1R from Hoplobatrachus rugulosus (Dicroglossidae) and magainin-AM1, magainin-AM2, caerulein precursor fragment (CPF-AM1) and peptide glycine leucine amide (PGLa-AM1) from Xenopus amieti (Pipidae) on GLP-1 secretion from GLUTag cells. Tigerinin-1R showed the highest potency producing a significant (P < 0.05) increase in GLP-1 release at a concentration of 0.1 nM for the cyclic peptide and 0.3 nM for the reduced form. All peptides from X amieti significantly (P < 0.05) stimulated GLP-1 release at concentrations >= 300 nM with magainin-AM2 exhibiting the greatest potency (minimum concentration producing a significant stimulation = 1 nM). The maximum stimulatory response (3.2-fold of basal rate, P < 0.001) was produced by CPF-AM1 at a concentration of 3 mu M. No peptide stimulated release of the cytosolic enzyme, lactate dehydrogenase from GLUTag cells at concentrations up to 3 mu M indicating that the integrity of the plasma membrane had been preserved. The data indicate that frog skin peptides, by stimulating GLP-1 release as well as direct effects on insulin secretion, show therapeutic potential as agents for the treatment of type 2 diabetes. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.