Frog skin peptides (tigerinin-1R, magainin-AM1, -AM2, CPF-AM1, and PGla-AM1) stimulate secretion of glucagon-like peptide 1 (GLP-1) by GLUTag cells

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. μM. No peptide stimulated release of the cytosolic enzyme, lactate dehydrogenase from GLUTag cells at concentrations up to 3. μM 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.